mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) for which this fold was named perform only a small fraction of the activities included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases which can catalyze the hydrolysis of a wide range of beta-lactam antibiotics, hydroxyacylglutathione hydrolases (also called glyoxalase II) which hydrolyze S-d-lactoylglutathione to d-lactate in the second step of the glycoxlase system, AHL lactonases which catalyze the hydrolysis and opening of the homoserine lactone rings of acyl homoserine lactones (AHLs), persulfide dioxygenase which catalyze the oxidation of glutathione persulfide to glutathione and persulfite in the mitochondria, flavodiiron proteins which catalyze the reduction of oxygen and/or nitric oxide to water or nitrous oxide respectively, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J which has both 5'-3' exoribonucleolytic and endonucleolytic activity and ribonuclease Z which catalyzes the endonucleolytic removal of the 3' extension of the majority of tRNA precursors, cyclic nucleotide phosphodiesterases which decompose cyclic adenosine and guanosine 3', 5'-monophosphate (cAMP and cGMP) respectively, insecticide hydrolases, and proteins required for natural transformation competence. The diversity of biological roles is reflected in variations in the active site metallo-chemistry, for example classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, human persulfide dioxygenase ETHE1 is a mono-iron binding member of the superfamily; Arabidopsis thaliana hydroxyacylglutathione hydrolases incorporates iron, manganese, and zinc in its dinuclear metal binding site, and flavodiiron proteins contains a diiron site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIEqDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDWyhgVDG 95
Cdd:cd07721   14 YLIEDDDGLTLIDTGLPGSAKRILKALR-ELGLSPKDIRRILLTHGHIDHIGSLAALKEAPGAPVYAHEREAPY---LEG 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  96 WLMHLTDLLLAAWMANRLKKPWRNLWysralnPDHKLNDGECIPEFPEWVVLETPGHTDRDLSVYHAEQGILYVADLMVE 175
Cdd:cd07721   90 EKPYPPPVRLGLLGLLSPLLPVKPVP------VDRTLEDGDTLDLAGGLRVIHTPGHTPGHISLYLEEDGVLIAGDALVT 163

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 746499949 176 VKRKLIAPFPIFHPNKYRA--SLERVFHMQPTTLLLAHG 212
Cdd:cd07721  164 VGGELVPPPPPFTWDMEEAleSLRKLAELDPEVLAPGHG 202

uncharacterized subgroup which includes Bacillus subtilis yflN; MBL-fold metallo hydrolase domain; This subgroup includes the uncharacterized Bacillus subtilis yflN protein. Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIEqDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDWyhgVDG 95
Cdd:cd07721   14 YLIEDDDGLTLIDTGLPGSAKRILKALR-ELGLSPKDIRRILLTHGHIDHIGSLAALKEAPGAPVYAHEREAPY---LEG 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  96 WLMHLTDLLLAAWMANRLKKPWRNLWysralnPDHKLNDGECIPEFPEWVVLETPGHTDRDLSVYHAEQGILYVADLMVE 175
Cdd:cd07721   90 EKPYPPPVRLGLLGLLSPLLPVKPVP------VDRTLEDGDTLDLAGGLRVIHTPGHTPGHISLYLEEDGVLIAGDALVT 163

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 746499949 176 VKRKLIAPFPIFHPNKYRA--SLERVFHMQPTTLLLAHG 212
Cdd:cd07721  164 VGGELVPPPPPFTWDMEEAleSLRKLAELDPEVLAPGHG 202

Metallo-beta-lactamase superfamily; Apart from the beta-lactamases a number of other proteins contain this domain. These proteins include thiolesterases, members of the glyoxalase II family, that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid and a competence protein that is essential for natural transformation in Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the competence protein these proteins bind two zinc ions per molecule as cofactor.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949    15 MYLVEYPDKLLLLDGASRADISYLRRFIEQDLGrsfcDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDwyhgvd 94
Cdd:smart00849   2 SYLVRDDGGAILIDTGPGEAEDLLAELKKLGPK----KIDAIILTHGHPDHIGGLPELLEAPGAPVYAPEGTAE------ 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949    95 gwlmhltdlllaaWMANRLKKPWRNLWYSRALNPDHKLNDGECIP-EFPEWVVLETPGHTDRDLSVYHAEQGILYVAD-L 172
Cdd:smart00849  72 -------------LLKDLLALLGELGAEAEPAPPDRTLKDGDELDlGGGELEVIHTPGHTPGSIVLYLPEGKILFTGDlL 138

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 746499949   173 MVEVKRKLIAPFPIFHPNKYRASLERVFHMQPTTLLLAH 211
Cdd:smart00849 139 FAGGDGRTLVDGGDAAASDALESLLKLLKLLPKLVVPGH 177

quinoprotein relay system zinc metallohydrolase 2; By homology, members are Zn metallohydrolases in the same family as the SoxH protein associated with sulfate metabolism, Bacillus cereus beta-lactamase II (see PDB:1bc2), and, more distantly, hydroxyacylglutathione hydrolase (glyoxalase II). All members occur in genomes with both PQQ biosynthesis and a PQQ-dependent (quinoprotein) dehydrogenase that has a motif of two consecutive Cys residues (see TIGR03075). The Cys-Cys motif is associated with electron transfer by specialized cytochromes such as c551. All these genomes also include a fusion protein (TIGR04557) whose domains resemble SoxY and SoxZ from thiosulfate oxidation. A conserved Cys in this fusion protein aligns to the Cys residue in SoxY that carries sulfur cycle intermediates. In many genomes, the genes for PQQ biosynthesis enzymes, PQQ-dependent enzymes, their associated cytochromes, and members of this family are clustered. Note that one to three closely related Zn metallohydrolases may occur; this family represents a specific clade among them. Some members of this family have a short additional N-terminal domain with four conserved Cys residues. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949   29 GASRADISYLRRFIEQdlgRSfcDLKV--VVVTHMHPDHAGGAHRLRQlTGCQVVAAN---RDLDWYHgvDGWLMHLTDL 103
Cdd:TIGR04559  47 GGSRAEGEALLAAIRQ---RT--DLPIryVINTHVHPDHIFGNAAFRE-DGAEFVGHAklpRALAARG--EFYLASFARL 118

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 746499949  104 LLAAWMANRLKKPwrnlwySRALNPDHKLNDGECIPEFPEWvvleTPGHTDRDLSVYHAEQGILYVADL 172
Cdd:TIGR04559 119 LGEAFLGTEIVPP------TRLVADPLELDLGGRVLELTAW----PTAHTDNDLTVFDEKTGTLFTGDL 177

uncharacterized subgroup which includes Bacillus subtilis yflN; MBL-fold metallo hydrolase domain; This subgroup includes the uncharacterized Bacillus subtilis yflN protein. Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIEqDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDWyhgVDG 95
Cdd:cd07721   14 YLIEDDDGLTLIDTGLPGSAKRILKALR-ELGLSPKDIRRILLTHGHIDHIGSLAALKEAPGAPVYAHEREAPY---LEG 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  96 WLMHLTDLLLAAWMANRLKKPWRNLWysralnPDHKLNDGECIPEFPEWVVLETPGHTDRDLSVYHAEQGILYVADLMVE 175
Cdd:cd07721   90 EKPYPPPVRLGLLGLLSPLLPVKPVP------VDRTLEDGDTLDLAGGLRVIHTPGHTPGHISLYLEEDGVLIAGDALVT 163

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 746499949 176 VKRKLIAPFPIFHPNKYRA--SLERVFHMQPTTLLLAHG 212
Cdd:cd07721  164 VGGELVPPPPPFTWDMEEAleSLRKLAELDPEVLAPGHG 202

Metallo-beta-lactamase superfamily; Apart from the beta-lactamases a number of other proteins contain this domain. These proteins include thiolesterases, members of the glyoxalase II family, that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid and a competence protein that is essential for natural transformation in Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the competence protein these proteins bind two zinc ions per molecule as cofactor.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949    15 MYLVEYPDKLLLLDGASRADISYLRRFIEQDLGrsfcDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDwyhgvd 94
Cdd:smart00849   2 SYLVRDDGGAILIDTGPGEAEDLLAELKKLGPK----KIDAIILTHGHPDHIGGLPELLEAPGAPVYAPEGTAE------ 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949    95 gwlmhltdlllaaWMANRLKKPWRNLWYSRALNPDHKLNDGECIP-EFPEWVVLETPGHTDRDLSVYHAEQGILYVAD-L 172
Cdd:smart00849  72 -------------LLKDLLALLGELGAEAEPAPPDRTLKDGDELDlGGGELEVIHTPGHTPGSIVLYLPEGKILFTGDlL 138

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 746499949   173 MVEVKRKLIAPFPIFHPNKYRASLERVFHMQPTTLLLAH 211
Cdd:smart00849 139 FAGGDGRTLVDGGDAAASDALESLLKLLKLLPKLVVPGH 177

uncharacterized subgroup of the MBL-fold_metallo-hydrolase superfamily; MBL-fold metallo hydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) for which this fold was named perform only a small fraction of the activities included in this superfamily.Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  16 YLVEYPDKLLLLD-GAsrADISYLRRFIEQDLGRsfcDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDwyHGVD 94
Cdd:cd16278   21 YLLGAPDGVVVIDpGP--DDPAHLDALLAALGGG---RVSAILVTHTHRDHSPGAARLAERTGAPVRAFGPHRA--GGQD 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  95 gwlmhltdlllaawmanrlkkpwrnlwysRALNPDHKLNDGECIpEFPEW--VVLETPGHTDRDLSVYHAEQGILYVAD- 171
Cdd:cd16278   94 -----------------------------TDFAPDRPLADGEVI-EGGGLrlTVLHTPGHTSDHLCFALEDEGALFTGDh 143

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 746499949 172 LM-----VevkrklIAPfPIFHPNKYRASLERVFHMQPTTLLLAHGGE 214
Cdd:cd16278  144 VMgwsttV------IAP-PDGDLGDYLASLERLLALDDRLLLPGHGPP 184

mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) for which this fold was named perform only a small fraction of the activities included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases which can catalyze the hydrolysis of a wide range of beta-lactam antibiotics, hydroxyacylglutathione hydrolases (also called glyoxalase II) which hydrolyze S-d-lactoylglutathione to d-lactate in the second step of the glycoxlase system, AHL lactonases which catalyze the hydrolysis and opening of the homoserine lactone rings of acyl homoserine lactones (AHLs), persulfide dioxygenase which catalyze the oxidation of glutathione persulfide to glutathione and persulfite in the mitochondria, flavodiiron proteins which catalyze the reduction of oxygen and/or nitric oxide to water or nitrous oxide respectively, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J which has both 5'-3' exoribonucleolytic and endonucleolytic activity and ribonuclease Z which catalyzes the endonucleolytic removal of the 3' extension of the majority of tRNA precursors, cyclic nucleotide phosphodiesterases which decompose cyclic adenosine and guanosine 3', 5'-monophosphate (cAMP and cGMP) respectively, insecticide hydrolases, and proteins required for natural transformation competence. The diversity of biological roles is reflected in variations in the active site metallo-chemistry, for example classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, human persulfide dioxygenase ETHE1 is a mono-iron binding member of the superfamily; Arabidopsis thaliana hydroxyacylglutathione hydrolases incorporates iron, manganese, and zinc in its dinuclear metal binding site, and flavodiiron proteins contains a diiron site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  16 YLVEYPDK-LLLLD-GASraDISYLRRFIEqdlgRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDWyhgv 93
Cdd:cd06262   13 YLVSDEEGeAILIDpGAG--ALEKILEAIE----ELGLKIKAILLTHGHFDHIGGLAELKEAPGAPVYIHEADAEL---- 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  94 dgwlmhLTDLLLAAWMANRLKKPwrnlwysrALNPDHKLNDGECI-PEFPEWVVLETPGHTDRDLSVYHAEQGILYVADL 172
Cdd:cd06262   83 ------LEDPELNLAFFGGGPLP--------PPEPDILLEDGDTIeLGGLELEVIHTPGHTPGSVCFYIEEEGVLFTGDT 148

uncharacterized subgroup of the MBL-fold_metallo-hydrolase superfamily; MBL-fold metallo hydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949   8 IQGYIQIMYLVEYPDKLLLLDgaSRADISYLRRfIEQDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAanrdl 87
Cdd:cd07743    4 IPGPTNIGVYVFGDKEALLID--SGLDEDAGRK-IRKILEELGWKLKAIINTHSHADHIGGNAYLQKKTGCKVYA----- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  88 dwyHGVDGWLMHLTDLLLAAWMANRLKKPWRNLWY-SRALNPDHKLNDGECIPEFPEWVVLETPGHTDRDLSVYHaEQGI 166
Cdd:cd07743   76 ---PKIEKAFIENPLLEPSYLGGAYPPKELRNKFLmAKPSKVDDIIEEGELELGGVGLEIIPLPGHSFGQIGILT-PDGV 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 746499949 167 LYVADLMV--EVKRKLIAPFpIFHPNKYRASLERVFHMQPTTLLLAH 211
Cdd:cd07743  152 LFAGDALFgeEVLEKYGIPF-LYDVEEQLETLEKLEELDADYYVPGH 197

metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. B3 MBLs include Fluoribacter gormanii FEZ-1, Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) GOB-1, Stenotrophomonas Maltophilia L1, and Bradyrhizobium diazoefficiens BJP-1, Serratia marcescens SMB-1, and Pseudomonas Aeruginosa AIM-1. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIEQdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLD 88
Cdd:cd07708   25 YLIVTPQGNILIDGDMEQNAPMIKANIKK-LGFKFSDTKLILISHAHFDHAGGSAEIKKQTGAKVMAGAEDVS 96

uncharacterized subgroup of the MBL-fold_metallo-hydrolase superfamily; MBL-fold metallo hydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) for which this fold was named perform only a small fraction of the activities included in this superfamily.Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  54 KVVVVTHMHPDHAGGAHRLRQLtGCQVVAANRDLDWYHGVDGWLMHLTDLLLAAWMAN-RLKKPwrNLWYSRALNPDhkL 132
Cdd:cd16282   54 RYVVNTHYHGDHTLGNAAFADA-GAPIIAHENTREELAARGEAYLELMRRLGGDAMAGtELVLP--DRTFDDGLTLD--L 128

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949 133 NDGEcipefpewVVLET--PGHTDRDLSVYHAEQGILYVADLmVEVKRklIAPFPIFHPNKYRASLERVFHMQPTTLLLA 210
Cdd:cd16282  129 GGRT--------VELIHlgPAHTPGDLVVWLPEEGVLFAGDL-VFNGR--IPFLPDGSLAGWIAALDRLLALDATVVVPG 197

                 ..
gi 746499949 211 HG 212
Cdd:cd16282  198 HG 199

BJP-1, FEZ-1, GOB-1, Mbl1b and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; This subgroup of B3 subclass MBLs includes Bradyrhizobium diazoefficiens BJP-1, Fluoribacter gormanii FEZ-1, Elizabethkingia meningoseptica (Chryseobacterium meningosepticum) GOB-1, Caulobacter crescentus Mbl1b. MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIEQdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRD 86
Cdd:cd16288   25 YLITTPQGLILIDTGLESSAPMIKANIRK-LGFKPSDIKILLNSHAHLDHAGGLAALKKLTGAKLMASAED 94

Caulobacter crescentus Mbl1b and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup of Mbl1b-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 746499949  16 YLVEYPDKLLLLDGASRADISYLRRFIeQDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRD 86
Cdd:cd16310   25 YLITSNHGAILLDGGLEENAALIEQNI-KALGFKLSDIKIIINTHAHYDHAGGLAQLKADTGAKLWASRGD 94

hydroxyacylglutathione hydrolase, MBL-fold metallo-hydrolase domain; hydroxyacylglutathione hydrolase (EC 3.1.2.6, also known as, glyoxalase II; S-2-hydroxylacylglutathione hydrolase; hydroxyacylglutathione hydrolase; acetoacetylglutathione hydrolase). In the second step of the glycoxlase system this enzyme hydrolyzes S-d-lactoylglutathione to d-lactate and regenerates glutathione in the process. It has broad substrate specificity for glutathione thiol esters, hydrolyzing a number of these species to their corresponding carboxylic acids and reduced glutathione. It appears to hydrolyze 2-hydroxy thiol esters with greatest efficiency. It belongs to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  52 DLKVVVVTHMHPDHAGGAHRLRQLTG-CQVVAANRDldwyhgvdgwlmhltdlllaawmanrlkkpwrnlwysRALNPDH 130
Cdd:cd07723   43 TLTAILTTHHHWDHTGGNAELKALFPdAPVYGPAED-------------------------------------RIPGLDH 85

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 746499949 131 KLNDGECIPEFP-EWVVLETPGHTDRDLSVYHAEQGILYVAD 171
Cdd:cd07723   86 PVKDGDEIKLGGlEVKVLHTPGHTLGHICYYVPDEPALFTGD 127

Erythrobacter vulgaris EVM-1 and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup EVM-1-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 746499949  17 LVEYPDKLLLLDGASRADISYLRRFIEQdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVA 82
Cdd:cd16315   26 LITGDDGHVLIDSGTEEAAPLVLANIRK-LGFDPKDVRWLLSSHEHFDHVGGLAALQRATGARVAA 90

AIM-1, SMB-1, EVM-1, THIN-B and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; This subgroup of B3 subclass MBLs includes Pseudomonas Aeruginosa AIM-1, Serratia marcescens SMB-1, Erythrobacter vulgaris EVM-1, and Janthinobacterium lividum THIN-B. MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup of AIM-1-,SMB-1-, EVM-1-, THIN-B-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  17 LVEYPDKLLLLDGA---SRADI-SYLRRfieqdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVA 82
Cdd:cd16290   26 LITSPQGLILIDGAlpqSAPQIeANIRA-----LGFRLEDVKLILNSHAHFDHAGGIAALQRDSGATVAA 90

ETHE1 (PDO type I), persulfide dioxygenase A (PDOA, PDO type II) and related proteins; MBL-fold metallo-hydrolase domain; Persulfide dioxygenase (PDO, also known as sulfur dioxygenase, SDO, EC 1.13.11.18) is a non-heme iron-dependent oxygenase which catalyzes the oxidation of glutathione persulfide to glutathione and persulfite in the mitochondria. Mutations in ethe1 (the human PDO gene) are responsible for a rare autosomal recessive metabolic disorder called ethylmalonic encephalopathy. Arabidopsis thaliana ETHE1 is essential for embryo and endosperm development. Bacterial ETHE1-type PDOs are also called Type 1 PDOs. Type II PDOs (also called PDOAs), are mainly proteobacterial. These enzymes belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  51 CDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAANRDLDWYhgvdgwlmhltdlllaawmanrlkkpwrnlwysralnPDH 130
Cdd:cd07724   47 LKITYVLETHVHADHVSGARELAERTGAPIVIGEGAPASF-------------------------------------FDR 89

                         90       100
                 ....*....|....*....|....*...
gi 746499949 131 KLNDGECIP----EFpewVVLETPGHTD 154
Cdd:cd07724   90 LLKDGDVLElgnlTL---EVLHTPGHTP 114

Ribonuclease BN, tRNA processing enzyme [Translation, ribosomal structure and biogenesis];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 746499949  16 YLVEYPDKLLLLD---GAsradisyLRRFieQDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQ 74
Cdd:COG1234   22 YLLEAGGERLLIDcgeGT-------QRQL--LRAGLDPRDIDAIFITHLHGDHIAGLPGLLS 74

quinoprotein relay system zinc metallohydrolase 2; By homology, members are Zn metallohydrolases in the same family as the SoxH protein associated with sulfate metabolism, Bacillus cereus beta-lactamase II (see PDB:1bc2), and, more distantly, hydroxyacylglutathione hydrolase (glyoxalase II). All members occur in genomes with both PQQ biosynthesis and a PQQ-dependent (quinoprotein) dehydrogenase that has a motif of two consecutive Cys residues (see TIGR03075). The Cys-Cys motif is associated with electron transfer by specialized cytochromes such as c551. All these genomes also include a fusion protein (TIGR04557) whose domains resemble SoxY and SoxZ from thiosulfate oxidation. A conserved Cys in this fusion protein aligns to the Cys residue in SoxY that carries sulfur cycle intermediates. In many genomes, the genes for PQQ biosynthesis enzymes, PQQ-dependent enzymes, their associated cytochromes, and members of this family are clustered. Note that one to three closely related Zn metallohydrolases may occur; this family represents a specific clade among them. Some members of this family have a short additional N-terminal domain with four conserved Cys residues. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949   29 GASRADISYLRRFIEQdlgRSfcDLKV--VVVTHMHPDHAGGAHRLRQlTGCQVVAAN---RDLDWYHgvDGWLMHLTDL 103
Cdd:TIGR04559  47 GGSRAEGEALLAAIRQ---RT--DLPIryVINTHVHPDHIFGNAAFRE-DGAEFVGHAklpRALAARG--EFYLASFARL 118

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 746499949  104 LLAAWMANRLKKPwrnlwySRALNPDHKLNDGECIPEFPEWvvleTPGHTDRDLSVYHAEQGILYVADL 172
Cdd:TIGR04559 119 LGEAFLGTEIVPP------TRLVADPLELDLGGRVLELTAW----PTAHTDNDLTVFDEKTGTLFTGDL 177

Janthinobacterium lividum THIN-B and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup of THIN-B-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 746499949  17 LVEYPDKLLLLDGASRADISYLRRFIEQdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVAA 83
Cdd:cd16312   26 LVTSPQGHVLLDGALPQSAPLIIANIEA-LGFRIEDVKLILNSHAHWDHAGGIAALQKASGATVAAS 91

Janthinobacterium lividum THIN-B2 and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup of THIN-B2-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 746499949  17 LVEYPDKLLLLDGASRADISYLRRFIEQdLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVA---ANRDL 87
Cdd:cd16311   26 LVTSPQGHVLVDGGLPESAPKIIANIEA-LGFRIEDVKLILNSHGHIDHAGGLAELQRRSGALVAAspsAALDL 98

Pseudomonas pseudoalcaligenes organophosphorus hydrolase C2, and related proteins; MBL-fold metallo hydrolase domain; Pseudomonas pseudoalcaligenes OPHC2 is a thermostable organophosphorus hydrolase which a broad substrate activity spectrum: it hydrolyzes various phosphotriesters, esters, and a lactone. This subgroup also includes Pseudomonas oleovorans PoOPH which exhibits high lactonase and esterase activities, and latent PTE activity. However, double mutations His250Ile/Ile263Trp switch PoOPH into an efficient and thermostable PTE. Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 746499949  16 YLVEYPDKLLLLD-GASRADISYLRRFIE--QDLGRSFCDLKVVVVTHMHPDHAGG 68
Cdd:cd07720   52 FLVRTGGRLILVDtGAGGLFGPTAGKLLAnlAAAGIDPEDIDDVLLTHLHPDHIGG 107

Ribonuclease Z; MBL-fold metallo-hydrolase domain; The tRNA maturase RNase Z (also known as tRNase Z or 3' tRNase) catalyzes the endonucleolytic removal of the 3' extension of the majority of tRNA precursors. Two forms of RNase Z exist in eukaryotes, one long (ELAC2) and one short form (ELAC1), the former may have resulted from a duplication of the shorter enzyme. Only the short form exists in bacteria. It includes the C-terminus of human ELAC2 and Escherichia coli zinc phosphodiesterase (ZiPD, also known as ecoZ, tRNase Z, or RNase BN) is a 3' tRNA-processing endonuclease, encoded by the elaC gene. Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 746499949  16 YLVEYPDKLLLLDgASRADISYLRRfieqdLGRSFCDLKVVVVTHMHPDHAGG 68
Cdd:cd16272   20 YLLETGGTRILLD-CGEGTVYRLLK-----AGVDPDKLDAIFLSHFHLDHIGG 66

Pseudomonas Aeruginosa AIM-1 and related metallo-beta-lactamases, subclass B3; MBL-fold metallo-hydrolase domain; MBLs (class B of the Ambler beta-lactamase classification) are a diverse group of metallo-enzymes that are capable of catalyzing the hydrolysis of a wide range of beta-lactam antibiotics. MBLs have been divided into three subclasses B1, B2 and B3, based on sequence/structural relationships and substrates, with the B1 and B2 MBLs being most closely related to each other. This subgroup AIM-1-like MBLs belongs to the B3 subclass. Subclass B3 enzymes are most active with two zinc ions bound in the active site, and have a broad-spectrum substrate profile. These B3 enzymes have a modified Zn2/DCH site (Asp-His-His).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 746499949  17 LVEYPDKLLLLDGASRADISYLRRFIeQDLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTGCQVVA 82
Cdd:cd16314   26 LVTSDAGHILIDGGTDKAAPLIEANI-RALGFRPEDVRYIVSSHEHFDHAGGIARLQRATGAPVVA 90

uncharacterized human metallo-beta-lactamase domain-containing protein 1 and related proteins; MBL-fold metallo hydrolase domain; Includes the MBL-fold metallo hydrolase domain of uncharacterized human MBLAC1 and related proteins. Members of this subgroup belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 746499949  17 LVEYPDKLLLLDGASRADisylRRFIEQ---DLGRSFCDLKVVVVTHMHPDHAGGAHRLRQLTgcqvvaanrdldWYHGV 93
Cdd:cd07711   26 LIKDGGKNILVDTGTPWD----RDLLLKalaEHGLSPEDIDYVVLTHGHPDHIGNLNLFPNAT------------VIVGW 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 746499949  94 DGWLMHltdlllaaWMANRLKKPWRnlwysraLNPDHKLNdgecipefpewvVLETPGHTDRDLSV 159
Cdd:cd07711   90 DICGDS--------YDDHSLEEGDG-------YEIDENVE------------VIPTPGHTPEDVSV 128

uncharacterized subgroup of the MBL-fold_metallo-hydrolase superfamily; MBL-fold metallo hydrolase domain; Members of the MBL-fold metallohydrolase superfamily are mainly hydrolytic enzymes which carry out a variety of biological functions. The class B metal beta-lactamases (MBLs) from which this fold was named are only a small fraction of the activities which are included in this superfamily. Activities carried out by superfamily members include class B beta-lactamases, hydroxyacylglutathione hydrolases, AHL (acyl homoserine lactone) lactonases, persulfide dioxygenases, flavodiiron proteins, cleavage and polyadenylation specificity factors such as the Int9 and Int11 subunits of Integrator, Sdsa1-like and AtsA-like arylsulfatases, 5'-exonucleases human SNM1A and yeast Pso2p, ribonuclease J and ribonuclease Z, cyclic nucleotide phosphodiesterases, insecticide hydrolases, and proteins required for natural transformation competence. Classical members of the superfamily are di-, or less commonly mono-, zinc-ion-dependent hydrolases, however the diversity of biological roles is reflected in variations in the active site metallo-chemistry.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 746499949  17 LVEYPDKLLLLD-GASRADI-----SYLRRFIE----------------QDLGRSFCDLKVVVVTHMHPDHAGGAH 70
Cdd:cd07742   23 LVETDDGLVLVDtGFGLADVadpkrRLGGPFRRllrprldedetavrqiEALGFDPSDVRHIVLTHLDLDHAGGLA 98