Ligand-binding SRPBCC domain of Micromonospora echinospora CalC and related proteins; This subfamily includes Micromonospora echinospora CalC (MeCalC) and related proteins. These proteins belong to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. MeCalC confers resistance to the enediyne, calicheamicin gamma 1 (CLM). Enediyne antibiotics are antitumor agents. Enediynes have an in vitro and in vivo role as DNA damaging agents; they consist of a DNA recognition unit (e.g., aryltetrasaccharide of CLM), an activating component (e.g., methyl trisulfide of CLM), which promotes cycloaromatization, and the enediyne warhead which cycloaromatizes to a reactive diradical species, resulting in oxidative strand cleavage of the targeted DNA sequence. MeCalC confers resistance to CLM by a self sacrificing mechanism: the transient enediyne diradical species abstracts a CalC Gly Calpha-hydrogen, thereby quenching the reactive enediyne moiety, and generating a CalC Gly Calpha radical. This radical then reacts with oxygen, leading to oxidative site-specific proteolysis of CalC. This antibiotic-induced proteolysis of CalC results in inactivation of both CalC and the highly reactive diradical species. CalC has also been shown to inactivate two other enediynes, shishijimicin and namenamicin. The crucial Gly of the MeCalC CLM resistance mechanism is contained in a loop (L1) which is displaced when CLM is bound, this Gly is not conserved in this subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550   8 AIHHHVVVNAPIERAFAVFTTRFGDFKPREHNLLAIPITETVFECHAGGHIYDRGVDGSVCKWARVLVYEPPSRVLFTWD 87
Cdd:cd08891    1 PVRKSVTVPAPPERAFEVFTEGFGAWWPPEYHFVFSPGAEVVFEPRAGGRWYEIGEDGTECEWGTVLAWEPPSRLVFTWQ 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550  88 IGPTWRPETDLAktSEVEVRFTAQSAETTRVDLEHRHLDRHGPGWESVADGVDSEAGWPLYLRRYTDLLC 157
Cdd:cd08891   81 INADWRPDPDKA--SEVEVRFEAVGAEGTRVELEHRGFERHGDGWEAAAMRMGYDGGWPLLLERYAAAAE 148

Ligand-binding SRPBCC domain of Micromonospora echinospora CalC and related proteins; This subfamily includes Micromonospora echinospora CalC (MeCalC) and related proteins. These proteins belong to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. MeCalC confers resistance to the enediyne, calicheamicin gamma 1 (CLM). Enediyne antibiotics are antitumor agents. Enediynes have an in vitro and in vivo role as DNA damaging agents; they consist of a DNA recognition unit (e.g., aryltetrasaccharide of CLM), an activating component (e.g., methyl trisulfide of CLM), which promotes cycloaromatization, and the enediyne warhead which cycloaromatizes to a reactive diradical species, resulting in oxidative strand cleavage of the targeted DNA sequence. MeCalC confers resistance to CLM by a self sacrificing mechanism: the transient enediyne diradical species abstracts a CalC Gly Calpha-hydrogen, thereby quenching the reactive enediyne moiety, and generating a CalC Gly Calpha radical. This radical then reacts with oxygen, leading to oxidative site-specific proteolysis of CalC. This antibiotic-induced proteolysis of CalC results in inactivation of both CalC and the highly reactive diradical species. CalC has also been shown to inactivate two other enediynes, shishijimicin and namenamicin. The crucial Gly of the MeCalC CLM resistance mechanism is contained in a loop (L1) which is displaced when CLM is bound, this Gly is not conserved in this subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550   8 AIHHHVVVNAPIERAFAVFTTRFGDFKPREHNLLAIPITETVFECHAGGHIYDRGVDGSVCKWARVLVYEPPSRVLFTWD 87
Cdd:cd08891    1 PVRKSVTVPAPPERAFEVFTEGFGAWWPPEYHFVFSPGAEVVFEPRAGGRWYEIGEDGTECEWGTVLAWEPPSRLVFTWQ 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550  88 IGPTWRPETDLAktSEVEVRFTAQSAETTRVDLEHRHLDRHGPGWESVADGVDSEAGWPLYLRRYTDLLC 157
Cdd:cd08891   81 INADWRPDPDKA--SEVEVRFEAVGAEGTRVELEHRGFERHGDGWEAAAMRMGYDGGWPLLLERYAAAAE 148

Activator of Hsp90 ATPase homolog 1-like protein; This family includes eukaryotic, prokaryotic and archaeal proteins that bear similarity to a C-terminal region of human activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1/p38). This protein is known to interact with the middle domain of Hsp90, and stimulate its ATPase activity. It is probably a general upregulator of Hsp90 function, particularly contributing to its efficiency in conditions of increased stress. p38 is also known to interact with the cytoplasmic domain of the VSV G protein, and may thus be involved in protein transport. It has also been reported as being underexpressed in Down's syndrome. This region is found repeated in two members of this family (Swiss:Q8XY04 and Swiss:Q6MH87). The structure of YndB from Bacillus subtilis showed the helix-grip fold consisting of a beta-sheet with two small and one long alpha-helix which form a hydrophobic cavity that preferentially binds lipid-like molecules. This structure confirms its similarity with the eukaryote protein Aha1 and its classification as a member of the AHSA1 family).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550   16 NAPIERAFAVFTTRfgdfkprehNLLA--IPITETVFECHAGGHI-YDRGVDGSVCKWA-RVLVYEPPSRVLFTWDIGpt 91
Cdd:pfam08327   1 DAPPERVFRALTDP---------ELLArwFTRTVAEMDLRPGGKFrFMRGPDGEEFGGNgTYLELVPPKRIVYTWRLD-- 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444895550   92 wrpETDLAKTSEVEVRFTAQSAEtTRVDLEHRHLDRHGpgwesvADGVDSEAGWPLYLRRYTDLL 156
Cdd:pfam08327  70 ---DWPEGGYSTVTVELEEVGGG-TRLTLTHTGEPAGE------KEEMGMEEGWEQSLDQLKALL 124

Ligand-binding SRPBCC domain of Micromonospora echinospora CalC and related proteins; This subfamily includes Micromonospora echinospora CalC (MeCalC) and related proteins. These proteins belong to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. MeCalC confers resistance to the enediyne, calicheamicin gamma 1 (CLM). Enediyne antibiotics are antitumor agents. Enediynes have an in vitro and in vivo role as DNA damaging agents; they consist of a DNA recognition unit (e.g., aryltetrasaccharide of CLM), an activating component (e.g., methyl trisulfide of CLM), which promotes cycloaromatization, and the enediyne warhead which cycloaromatizes to a reactive diradical species, resulting in oxidative strand cleavage of the targeted DNA sequence. MeCalC confers resistance to CLM by a self sacrificing mechanism: the transient enediyne diradical species abstracts a CalC Gly Calpha-hydrogen, thereby quenching the reactive enediyne moiety, and generating a CalC Gly Calpha radical. This radical then reacts with oxygen, leading to oxidative site-specific proteolysis of CalC. This antibiotic-induced proteolysis of CalC results in inactivation of both CalC and the highly reactive diradical species. CalC has also been shown to inactivate two other enediynes, shishijimicin and namenamicin. The crucial Gly of the MeCalC CLM resistance mechanism is contained in a loop (L1) which is displaced when CLM is bound, this Gly is not conserved in this subgroup.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550   8 AIHHHVVVNAPIERAFAVFTTRFGDFKPREHNLLAIPITETVFECHAGGHIYDRGVDGSVCKWARVLVYEPPSRVLFTWD 87
Cdd:cd08891    1 PVRKSVTVPAPPERAFEVFTEGFGAWWPPEYHFVFSPGAEVVFEPRAGGRWYEIGEDGTECEWGTVLAWEPPSRLVFTWQ 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550  88 IGPTWRPETDLAktSEVEVRFTAQSAETTRVDLEHRHLDRHGPGWESVADGVDSEAGWPLYLRRYTDLLC 157
Cdd:cd08891   81 INADWRPDPDKA--SEVEVRFEAVGAEGTRVELEHRGFERHGDGWEAAAMRMGYDGGWPLLLERYAAAAE 148

Putative hydrophobic ligand-binding SRPBCC domain of Micromonospora echinospora CalC, human Aha1, and related proteins; This family includes the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of Micromonospora echinospora CalC, human Aha1, and related proteins. Proteins in this group belong to the SRPBCC domain superfamily of proteins, which bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. MeCalC confers resistance to the enediyne, calicheamicin gamma 1 (CLM), by a self sacrificing mechanism which results in inactivation of both CalC and the highly reactive diradical enediyne species. MeCalC can also inactivate two other enediynes, shishijimicin and namenamicin. A crucial Gly of the MeCalC CLM resistance mechanism is not conserved in this subgroup. This family also includes the C-terminal, Bet v1-like domain of Aha1, one of several co-chaperones, which regulate the dimeric chaperone Hsp90. Aha1 promotes dimerization of the N-terminal domains of Hsp90, and stimulates its low intrinsic ATPase activity, and may regulate the dwell time of Hsp90 with client proteins. Aha1 can act as either a positive or negative regulator of chaperone-dependent activation, depending on the client protein, but the mechanisms by which these opposing functions are achieved are unclear. Aha1 is upregulated in a number of tumor lines co-incident with the activation of several signaling kinases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444895550   9 IHHHVVVNAPIERAFAVFTTRfgdfkprehNLLAI---PITETVFECHAGGHIY-----DRGVDGSVckWARVLVYEPPS 80
Cdd:cd07814    2 ITIEREFDAPPELVWRALTDP---------ELLAQwfgPTTTAEMDLRVGGRWFffmtgPDGEEGWV--SGEVLEVEPPR 70

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 444895550  81 RVLFTWDIGPTWRPEtdlakTSEVEVRFTAQsAETTRVDLEHRHLDrHGPGWESVADGVdsEAGWPLYLRRYTDLL 156
Cdd:cd07814   71 RLVFTWAFSDETPGP-----ETTVTVTLEET-GGGTRLTLTHSGFP-EEDAEQEAREGM--EEGWTGTLDRLKALL 137

Putative hydrophobic ligand-binding SRPBCC domain of an uncharacterized subgroup of CalC- and Aha1-like proteins; SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain of a functionally uncharacterized subgroup of CalC- and Aha1-like proteins. This group shows similarity to the SRPBCC domains of Micromonospora echinospora CalC (a protein which confers resistance to enediynes) and human Aha1 (one of several co-chaperones which regulate the dimeric chaperone Hsp90), and belongs to the SRPBCC domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket and they bind diverse ligands.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 444895550  72 RVLVYEPPSRVLFTWDIGptwrpetdlAKTSEVEVRFTAQsAETTRVDLEHRHLDR------HGPGWE 133
Cdd:cd08899   68 TILACEPPRLLAFTWGEG---------GGESEVRFELAPE-GDGTRLTLTHRLLDErfgagaVGAGWH 125