haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to the Pseudomonas aeruginosa PA0065; 5'-nucleotidases dephosphorylate nucleoside 5'-monophosphates to nucleosides and inorganic phosphate. Purified Pseudomonas aeruginosa PA0065 displayed high activity toward 5'-UMP and 5'-IMP, significant activity against 5'-XMP and 5'-TMP, and low activity against 5'-CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKEYYKFEDKKAKEAVEKYREYFADKGIFENK 86
Cdd:cd04302    2 ILFDLDGTLTDSAEGITASVQYALEELGIPVpDESELRRFIGPPLEDSFRELLPFDEEEAQRAVDAYREYYKEKGLFENE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  87 IYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVkDKDKVIMV 166
Cdd:cd04302   82 VYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGI-APEQAVMI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 489531067 167 GDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:cd04302  161 GDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATYIVETPAELLELL 209

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to the Pseudomonas aeruginosa PA0065; 5'-nucleotidases dephosphorylate nucleoside 5'-monophosphates to nucleosides and inorganic phosphate. Purified Pseudomonas aeruginosa PA0065 displayed high activity toward 5'-UMP and 5'-IMP, significant activity against 5'-XMP and 5'-TMP, and low activity against 5'-CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKEYYKFEDKKAKEAVEKYREYFADKGIFENK 86
Cdd:cd04302    2 ILFDLDGTLTDSAEGITASVQYALEELGIPVpDESELRRFIGPPLEDSFRELLPFDEEEAQRAVDAYREYYKEKGLFENE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  87 IYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVkDKDKVIMV 166
Cdd:cd04302   82 VYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGI-APEQAVMI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 489531067 167 GDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:cd04302  161 GDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATYIVETPAELLELL 209

Haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKEYYK--FEDKKAKEAVEKYREYFADKGIfe 84
Cdd:pfam13419   1 IIFDFDGTLLDTEELIIKSFNYLLEEFGYGElSEEEILKFIGLPLREIFRYLGVseDEEEKIEFYLRKYNEELHDKLV-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   85 nKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKdKDKVI 164
Cdd:pfam13419  79 -KPYPGIKELLEELKEQGYKLGIVTSKSRENVEEFLKQLGLEDYFDVIVGGDDVEGKKPDPDPILKALEQLGLK-PEEVI 156

                         170       180
                  ....*....|....*....|..
gi 489531067  165 MVGDRKYDIIGAKKIGIDSIGV 186
Cdd:pfam13419 157 YVGDSPRDIEAAKNAGIKVIAV 178

2-phosphoglycolate phosphatase, prokaryotic; PGP is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In Ralstonia (Alcaligenes) eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO. The only other pertinent experimental evidence concerns the gene from E. coli. The in vitro activity of the Ralstonia and Escherichia enzymes was determined with crude cell extracts of strains containing PGP on expression plasmids and compared to controls. In E. coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the E. coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). The E. coli enzyme is not expressed under normal laboratory conditions; the pathway to which it belongs has not been determined. In fact, the possibility exists, although unlikely, that the E. coli enzyme and others within this equivalog have as their physiological substrate another, closely related molecule. The other seed chosen for this model, from Xylella fastidiosa has no experimental evidence, but is a plant pathogen and thus may obtain phosphoglycolate from its host. This model has been restricted to encompass only proteobacteria as no related PGP has been verified outside of this clade. Sequences from Aquifex aeolicus and Treponema pallidum fall between the trusted and noise cutoffs. Just below the noise cutoff is a gene which is part of the operon for the biosynthesis of the blue pigment, indigoidine, from Erwinia (Pectobacterium) chrysanthemi, a plant pathogen. It does not seem likely, considering the proposed biosynthetic mechanism, that the dephosphorylation of phosphoglycolate or a closely related compound is required. Possibly, this gene is fortuitously located in this operon, or has an indirect relationship to the necessity for the biosynthesis of this compound. Sequences from 11 species have been annotated as PGP or putative PGP but fall below the noise cutoff. None of these have experimental validation. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes (pfam00702). [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIG---PPLHDTFKEYYKFE--DKKAKEAVEKYREYFADKG 81
Cdd:TIGR01449   1 VLFDLDGTLVDSAPDIAAAVNMALAALGLPPaTLARVIGFIGngvPVLMERVLAWAGQEpdAQRVAELRKLFDRHYEEVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   82 IFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKDKD 161
Cdd:TIGR01449  81 GELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDSLAQRKPHPDPLLLAAERLGVAPQQ 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 489531067  162 KViMVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:TIGR01449 161 MV-YVGDSRVDIQAARAAGCPSVLLTYGYRYGEAIDLLPPDVLYDSLNELPPLL 213

haloacid dehalogenase (HAD)-like 5'-nucleotidases similar to the Pseudomonas aeruginosa PA0065; 5'-nucleotidases dephosphorylate nucleoside 5'-monophosphates to nucleosides and inorganic phosphate. Purified Pseudomonas aeruginosa PA0065 displayed high activity toward 5'-UMP and 5'-IMP, significant activity against 5'-XMP and 5'-TMP, and low activity against 5'-CMP. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKEYYKFEDKKAKEAVEKYREYFADKGIFENK 86
Cdd:cd04302    2 ILFDLDGTLTDSAEGITASVQYALEELGIPVpDESELRRFIGPPLEDSFRELLPFDEEEAQRAVDAYREYYKEKGLFENE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  87 IYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVkDKDKVIMV 166
Cdd:cd04302   82 VYPGIPELLEKLKAAGYRLYVATSKPEVFARRILEHFGLDEYFDGIAGASLDGSRVHKADVIRYALDTLGI-APEQAVMI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 489531067 167 GDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:cd04302  161 GDRKHDIIGARANGIDSIGVLYGYGSEDELEEAGATYIVETPAELLELL 209

pyrophosphatase similar to Bacillus subtilis PpaX; This family includes Bacillus subtilis PpaX which hydrolyzes pyrophosphate formed during serine-46-phosphorylated HPr (P-Ser-HPr) dephosphorylation by the bifunctional enzyme HPr kinase/phosphorylase. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   5 YEIVLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKeyyKFEDKKAKEAVEKYREYFADKGIF 83
Cdd:cd02616    1 ITTILFDLDGTLIDTNELIIKSFNHTLKEYGLEGyTREEVLPFIGPPLRETFE---KIDPDKLEDMVEEFRKYYREHNDD 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  84 ENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKdKDKV 163
Cdd:cd02616   78 LTKEYPGVYETLARLKSQGIKLGVVTTKLRETALKGLKLLGLDKYFDVIVGGDDVTHHKPDPEPVLKALELLGAE-PEEA 156

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 489531067 164 IMVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDI 214
Cdd:cd02616  157 LMVGDSPHDILAGKNAGVKTVGVTWGYKGREYLKAFNPDFIIDKMSDLLTI 207

pyrophosphatase PpaX; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIGPPLHDTFKEYykfEDKKAKEAVEKYREYFADKGIFENK 86
Cdd:PRK13288   6 VLFDLDGTLINTNELIISSFLHTLKTYYPNQyKREDVLPFIGPSLHDTFSKI---DESKVEEMITTYREFNHEHHDELVT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  87 IYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGsnLDGTRVNK--NEVIQYVLDLCNVKdKDKVI 164
Cdd:PRK13288  83 EYETVYETLKTLKKQGYKLGIVTTKMRDTVEMGLKLTGLDEFFDVVIT--LDDVEHAKpdPEPVLKALELLGAK-PEEAL 159

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 489531067 165 MVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:PRK13288 160 MVGDNHHDILAGKNAGTKTAGVAWTIKGREYLEQYKPDFMLDKMSDLLAIV 210

Escherichia coli Gph phosphoglycolate phosphatase and related proteins; belongs to the haloacid dehalogenase-like superfamily; Phosphoglycolate phosphatase (PGP; EC 3.1.3.18) catalyzes the conversion of 2-phosphoglycolate into glycolate and phosphate. Members of this family belong to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase (C-Cl bond hydrolysis), azetidine hydrolase (C-N bond hydrolysis); phosphonoacetaldehyde hydrolase (C-P bond hydrolysis), phosphoserine phosphatase and phosphomannomutase (CO-P bond hydrolysis), P-type ATPases (PO-P bond hydrolysis) and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIG---PPL-HDTFKEYYKFEDKKA--KEAVEKYREYFADK 80
Cdd:cd16417    2 VAFDLDGTLVDSAPDLAEAANAMLAALGLPPlPEETVRTWIGngaDVLvERALTGAREAEPDEElfKEARALFDRHYAET 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  81 GIFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNldgTRVNKN---EVIQYVLDLCNV 157
Cdd:cd16417   82 LSVHSHLYPGVKEGLAALKAQGYPLACVTNKPERFVAPLLEALGISDYFSLVLGGD---SLPEKKpdpAPLLHACEKLGI 158

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 489531067 158 kDKDKVIMVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIvenVESIKDIL 215
Cdd:cd16417  159 -APAQMLMVGDSRNDILAARAAGCPSVGLTYGYNYGEDIAASGPDAV---IDSLAELL 212

haloacid dehalogenase-like hydrolase; This family is structurally different from the alpha/beta hydrolase family (pfam00561). This family includes L-2-haloacid dehalogenase, epoxide hydrolases and phosphatases. The structure of the family consists of two domains. One is an inserted four helix bundle, which is the least well conserved region of the alignment, between residues 16 and 96 of Swiss:P24069. The rest of the fold is composed of the core alpha/beta domain. Those members with the characteriztic DxD triad at the N-terminus are probably phosphatidylglycerolphosphate (PGP) phosphatases involved in cardiolipin biosynthesis in the mitochondria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    5 YEIVLFDLDGTLTDPKEGITKSIQYSLNSFGIKEDLENLDQFIGPPLHDTFKEY----YKFEDKKAKEAVEKYREYFADK 80
Cdd:pfam00702   1 IKAVVFDLDGTLTDGEPVVTEAIAELASEHPLAKAIVAAAEDLPIPVEDFTARLllgkRDWLEELDILRGLVETLEAEGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   81 GIF------------ENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVI 148
Cdd:pfam00702  81 TVVlvellgvialadELKLYPGAAEALKALKERGIKVAILTGDNPEAAEALLRLLGLDDYFDVVISGDDVGVGKPKPEIY 160

                         170       180       190
                  ....*....|....*....|....*....|..
gi 489531067  149 QYVLDLCNVKdKDKVIMVGDRKYDIIGAKKIG 180
Cdd:pfam00702 161 LAALERLGVK-PEEVLMVGDGVNDIPAAKAAG 191

phosphoglycolate phosphatase, similar to Synechococcus elongates phosphoglycolate phosphatase PGP/CbbZ; Phosphoglycolate phosphatase catalyzes the dephosphorylation of phosphoglycolate; its activity requires divalent cations, especially Mg++. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDpKEGITKSIQYSLNS-FGIK----EDLENLDQFigpplhdTFKEYYKFED----KKAKEAVEKYREYFA 78
Cdd:cd04303    2 IIFDFDGTLAD-SFPWFLSILNQLAArHGFKtvdeEEIEQLRQL-------SSREILKQLGvplwKLPLIAKDFRRLMAE 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  79 DkgIFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGtrvnKNEVIQYVLDLCNvK 158
Cdd:cd04303   74 A--APELALFPGVEDMLRALHARGVRLAVVSSNSEENIRRVLGPEELISLFAVIEGSSLFG----KAKKIRRVLRRTK-I 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 489531067 159 DKDKVIMVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKD 213
Cdd:cd04303  147 TAAQVIYVGDETRDIEAARKVGLAFAAVSWGYAKPEVLKALAPDHMLEDPEDLIQ 201

2-phosphoglycolate phosphatase, prokaryotic; PGP is an essential enzyme in the glycolate salvage pathway in higher organisms (photorespiration in plants). Phosphoglycolate results from the oxidase activity of RubisCO in the Calvin cycle when concentrations of carbon dioxide are low relative to oxygen. In Ralstonia (Alcaligenes) eutropha and Rhodobacter sphaeroides, the PGP gene (CbbZ) is located on an operon along with other Calvin cycle enzymes including RubisCO. The only other pertinent experimental evidence concerns the gene from E. coli. The in vitro activity of the Ralstonia and Escherichia enzymes was determined with crude cell extracts of strains containing PGP on expression plasmids and compared to controls. In E. coli, however, there does not appear to be a functional Calvin cycle (RubisCO is absent), although the E. coli PGP gene (gph) is on the same operon (dam) with ribulose-5-phosphate-3-epimerase (rpe), a gene in the pentose-phosphate pathway (along with other, unrelated genes). The E. coli enzyme is not expressed under normal laboratory conditions; the pathway to which it belongs has not been determined. In fact, the possibility exists, although unlikely, that the E. coli enzyme and others within this equivalog have as their physiological substrate another, closely related molecule. The other seed chosen for this model, from Xylella fastidiosa has no experimental evidence, but is a plant pathogen and thus may obtain phosphoglycolate from its host. This model has been restricted to encompass only proteobacteria as no related PGP has been verified outside of this clade. Sequences from Aquifex aeolicus and Treponema pallidum fall between the trusted and noise cutoffs. Just below the noise cutoff is a gene which is part of the operon for the biosynthesis of the blue pigment, indigoidine, from Erwinia (Pectobacterium) chrysanthemi, a plant pathogen. It does not seem likely, considering the proposed biosynthetic mechanism, that the dephosphorylation of phosphoglycolate or a closely related compound is required. Possibly, this gene is fortuitously located in this operon, or has an indirect relationship to the necessity for the biosynthesis of this compound. Sequences from 11 species have been annotated as PGP or putative PGP but fall below the noise cutoff. None of these have experimental validation. This enzyme is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolase enzymes (pfam00702). [Energy metabolism, Sugars]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    8 VLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIG---PPLHDTFKEYYKFE--DKKAKEAVEKYREYFADKG 81
Cdd:TIGR01449   1 VLFDLDGTLVDSAPDIAAAVNMALAALGLPPaTLARVIGFIGngvPVLMERVLAWAGQEpdAQRVAELRKLFDRHYEEVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   82 IFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKDKD 161
Cdd:TIGR01449  81 GELTSVFPGVEATLGALRAKGLRLGLVTNKPTPLARPLLELLGLAKYFSVLIGGDSLAQRKPHPDPLLLAAERLGVAPQQ 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 489531067  162 KViMVGDRKYDIIGAKKIGIDSIGVLYGYGSFEEISESEPTYIVENVESIKDIL 215
Cdd:TIGR01449 161 MV-YVGDSRVDIQAARAAGCPSVLLTYGYRYGEAIDLLPPDVLYDSLNELPPLL 213

Haloacid dehalogenase-like hydrolases; The haloacid dehalogenase-like (HAD) superfamily includes L-2-haloacid dehalogenase, epoxide hydrolase, phosphoserine phosphatase, phosphomannomutase, phosphoglycolate phosphatase, P-type ATPase, and many others. This superfamily includes a variety of enzymes that catalyze the cleavage of substrate C-Cl, P-C, and P-OP bonds via nucleophilic substitution pathways. All of which use a nucleophilic aspartate in their phosphoryl transfer reaction. They catalyze nucleophilic substitution reactions at phosphorus or carbon centers, using a conserved Asp carboxylate in covalent catalysis. All members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. Members of this superfamily are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  91 MKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVkDKDKVIMVGDRK 170
Cdd:cd01427   12 AVELLKRLRAAGIKLAIVTNRSREALRALLEKLGLGDLFDGIIGSDGGGTPKPKPKPLLLLLLKLGV-DPEEVLFVGDSE 90

                         90
                 ....*....|....*.
gi 489531067 171 YDIIGAKKIGIDSIGV 186
Cdd:cd01427   91 NDIEAARAAGGRTVAV 106

haloacid dehalogenase-like superfamily phosphoglycolate phosphatase, similar to Rhodobacter sphaeroides CbbZ; Phosphoglycolate phosphatase catalyzes the dephosphorylation of phosphoglycolate; its activity requires divalent cations, especially Mg++. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   7 IVLFDLDGTLTDPKEGITKSIQYSLNSFGIKE-DLENLDQFIG---PPL-HDTFKEYYKFEDKKAKEA-VEKYREYFADK 80
Cdd:cd07512    1 AVIFDLDGTLIDSAPDLHAALNAVLAAEGLAPlSLAEVRSFVGhgaPALiRRAFAAAGEDLDGPLHDAlLARFLDHYEAD 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  81 GIFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVkDK 160
Cdd:cd07512   81 PPGLTRPYPGVIEALERLRAAGWRLAICTNKPEAPARALLSALGLADLFAAVVGGDTLPQRKPDPAPLRAAIRRLGG-DV 159

                        170       180       190
                 ....*....|....*....|....*....|.
gi 489531067 161 DKVIMVGDRKYDIIGAKKIGIDSIGVLYGYG 191
Cdd:cd07512  160 SRALMVGDSETDAATARAAGVPFVLVTFGYR 190

haloacid dehalogenase-like hydrolase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    8 VLFDLDGTLTDpkegiTKSIQYSLNSFGIKEDLENLDQFIGPPLHDTFKEYYKFEDKKAKEAVEKY--------REYFAD 79
Cdd:pfam12710   1 ALFDLDGTLLD-----GDSLFLLIRALLRRGGPDLWRALLVLLLLALLRLLGRLSRAGARELLRALlaglpeedAAELER 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   80 KG--IFENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDID------------RYFKYIAGSNLDGTRVNKN 145
Cdd:pfam12710  76 FVaeVALPRLHPGALELLAAHRAAGDRVVVVTGGLRPLVEPVLAELGFDevlatelevddgRFTGELRLIGPPCAGEGKV 155

                         170       180
                  ....*....|....*....|....*....
gi 489531067  146 EVIQ-YVLDLCNVKDKDKVIMVGDRKYDI 173
Cdd:pfam12710 156 RRLRaWLAARGLGLDLADSVAYGDSPSDL 184

haloacid dehalogenase superfamily, subfamily IA, variant 3 with third motif having DD or ED; This model represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs. The subfamilies are defined based on the location and the observed or predicted fold of a so-called "capping domain", or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that representing it with a single model is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an aparrent phylogenetic bifurcation. Subfamily IA is still too broad to model, but cannot be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms: (1) hhhhsDxxx(x)D, (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily IA. Individual models were made based on seeds exhibiting only one of the variants each. Variant 3 (this model) is found in the enzymes beta-phosphoglucomutase (TIGR01990) and deoxyglucose-6-phosphatase, while many other enzymes of subfamily IA exhibit this variant as well as variant 1 (TIGR01549). These three variant models were created with the knowledge that there will be overlap among them - this is by design and serves the purpose of eliminating the overlap with models of more distantly related HAD subfamilies caused by an overly broad single model. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    7 IVLFDLDGTLTDPKEGITKSIQYSLNSFGIKEDLENLDQfigppLHDTFKEYYKFEDKKAKEAVEKYREYFAD--KGIFE 84
Cdd:TIGR01509   1 AILFDLDGVLVDTEFAIAKLINREELGLVPDELGVSAVG-----RLELALRRFKAQYGRTISPEDAQLLYKQLfyEQIEE 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   85 N---KIYENMKEILEMLYKNGKILLVATSKPTVfAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKdKD 161
Cdd:TIGR01509  76 EaklKPLPGVRALLEALRARGKKLALLTNSPRA-HKLVLALLGLRDLFDVVIDSSDVGLGKPDPDIYLQALKALGLE-PS 153

                         170       180
                  ....*....|....*....|....*
gi 489531067  162 KVIMVGDRKYDIIGAKKIGIDSIGV 186
Cdd:TIGR01509 154 ECVFVDDSPAGIEAAKAAGMHTVGV 178

UmpH/NagD family phosphatase, similar to Escherichia coli UmpH UMP phosphatase/NagD nucleotide phosphatase and Mycobacterium tuberculosis Rv1692 glycerol 3-phosphate phosphatase; Escherichia coli UmpH/NagD is a ribonucleoside tri-, di-, and monophosphatase with a preference for purines, it shows peak activity with UMP and functions in UMP-degradation. It is also an effective phosphatase with AMP, GMP and CMP. Mycobacterium tuberculosis phosphatase, Rv1692 is a glycerol 3-phosphate phosphatase. Rv1692 is the final enzyme involved in glycerophospholipid recycling/catabolism. This subfamily belongs to the UmpH/NagD phosphatase family, and to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 489531067 159 DKDKVIMVGDR-KYDIIGAKKIGIDSIGVLYGYGSFEEISESE--PTYIVENV 208
Cdd:cd07530  193 KSEETLMVGDRlDTDIAAGIAAGIDTLLVLTGVTTREDLAKPPyrPTYIVPSL 245

human N-acetylneuraminate-9-phosphate phosphatase, Escherichia coli house-cleaning phosphatase YjjG, and related phosphatases; N-acetylneuraminate-9- phosphatase (Neu5Ac-9-Pase; E.C. 3.1.3.29) catalyzes the dephosphorylation of N-acylneuraminate 9-phosphate during the synthesis of N-acetylneuraminate; Escherichia coli nucleotide phosphatase YjjG has a broad pyrimidine nucleotide activity spectrum and functions as an in vivo house-cleaning phosphatase for noncanonical pyrimidine nucleotides. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  85 NKIYENMKEILEMLYKNGKILLVaTSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDLCNVKdKDKVI 164
Cdd:cd04305    8 DTLLPGAKELLEELKKGYKLGII-TNGPTEVQWEKLEQLGIHKYFDHIVISEEVGVQKPNPEIFDYALNQLGVK-PEETL 85

                         90       100
                 ....*....|....*....|.
gi 489531067 165 MVGDRKY-DIIGAKKIGIDSI 184
Cdd:cd04305   86 MVGDSLEsDILGAKNAGIKTV 106

N-terminal lipase phosphatase domain of human soluble epoxide hydrolase, Escherichia coli YihX/HAD4 alpha-D-glucose 1-phosphate phosphatase, and related domains, may be inactive; This family includes the N-terminal phosphatase domain of human soluble epoxide hydrolase (sEH). sEH is a bifunctional enzyme with two distinct enzyme activities, the C-terminal domain has epoxide hydrolysis activity and the N-terminal domain (Ntermphos), which belongs to this family, has lipid phosphatase activity. The latter prefers mono-phosphate esters, and lysophosphatidic acids (LPAs) are the best natural substrates found to date. In addition this family includes Gallus gallus sEH and Xenopus sEH which appears to lack phosphatase activity, and Escherichia coli YihX/HAD4 which selectively hydrolyzes alpha-Glucose-1-P, phosphatase, has significant phosphatase activity against pyridoxal phosphate, and has low beta phosphoglucomutase activity. This family belongs to the haloacid dehalogenase-like (HAD) hydrolases, a large superfamily of diverse enzymes that catalyze carbon or phosphoryl group transfer reactions on a range of substrates, using an active site aspartate in nucleophilic catalysis. Members of this superfamily include 2-L-haloalkanoic acid dehalogenase, azetidine hydrolase, phosphonoacetaldehyde hydrolase, phosphoserine phosphatase, phosphomannomutase, P-type ATPases and many others. HAD hydrolases are found in all three kingdoms of life, and most genomes are predicted to contain multiple HAD-like proteins. Members possess a highly conserved alpha/beta core domain, and many also possess a small cap domain, the fold and function of which is variable. HAD hydrolases are sometimes referred to as belonging to the DDDD superfamily of phosphohydrolases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067   8 VLFDLDGTLTDPkeGITKSIQYSLNSFGIKEDLENLDQFIGPPLHD------TFKEYYkfedkkakEAVEKYREYFADKG 81
Cdd:cd02603    4 VLFDFGGVLIDP--DPAAAVARFEALTGEPSEFVLDTEGLAGAFLElergriTEEEFW--------EELREELGRPLSAE 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067  82 IFE------NKIYENMKEILEMLYKNG-KILLVATSKPTVFAETILRYFDIDRYFKYIAGSNLDGTRVNKNEVIQYVLDL 154
Cdd:cd02603   74 LFEelvlaaVDPNPEMLDLLEALRAKGyKVYLLSNTWPDHFKFQLELLPRRGDLFDGVVESCRLGVRKPDPEIYQLALER 153

                        170       180       190
                 ....*....|....*....|....*....|
gi 489531067 155 CNVKDKDkVIMVGDRKYDIIGAKKIGIDSI 184
Cdd:cd02603  154 LGVKPEE-VLFIDDREENVEAARALGIHAI 182

HAD-superfamily subfamily IB hydrolase, TIGR01490; This hypothetical equivalog is a member of the IB subfamily (TIGR01488) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The sequences modelled here are all bacterial. The IB subfamily includes the enzyme phosphoserine phosphatase (TIGR00338). Due to this relationship, several of these sequences have been annotated as "phosphoserine phosphatase related proteins," or "Phosphoserine phosphatase-family enzymes." There is presently no evidence that any of the enzymes in this model possess PSPase activity. OMNI|NTL01ML1250 is annotated as a "possible transferase," however this is due to the C-terminal domain found on this sequence which is homologous to a group of glycerol-phosphate acyltransferases (between trusted and noise to TIGR00530). A subset of these sequences including OMNI|CC1962, the Caulobacter crescentus CicA protein cluster together and may represent a separate equivalog. [Unknown function, Enzymes of unknown specificity]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489531067    7 IVLFDLDGTLTDP-------KEGITKSIQYSLNSFG------IKEDLENLDQFigpplhDTFKEYYK-FEDKKAKEAVEK 72
Cdd:TIGR01490   1 LAFFDFDGTLTAKdtlfiflKFLASKNILFEELRLPkvlarfEFFLNRGLDYM------AYYRAFALdALAGLLEEDVRA 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 489531067   73 YREYFADKGIfENKIYENMKEILEMLYKNGKILLVATSKPTVFAETILRYFDIDRY 128
Cdd:TIGR01490  75 IVEEFVNQKI-ESILYPEARDLIRWHKAEGHTIVLVSASLTILVKPLARILGIDNA 129