2GKD,2GKC


Conserved Protein Domain Family
SRPBCC_CalC

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cd08891: SRPBCC_CalC 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 176900
View PSSM: cd08891
Aligned: 24 rows
Threshold Bit Score: 136.716
Threshold Setting Gi: 119962398
Created: 31-Jul-2009
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 17 residues -Click on image for an interactive view with Cn3D
Feature 1:CLM binding site
Evidence:
  • Comment:Calicheamicin gamma-1 (CLM), is a core bicyclo (7.3.1) tridecadiynene moiety (enediyne warhead) attached to an aryltetrasaccharide chain.
  • Structure:2GKC_A; Micromonospora echinospora CalC binds CLM, contacts at 4A.
    View structure with Cn3D
  • Comment:CLM is bound with its DNA-recognition unit buried, its trisulfide trigger solvent exposed (faciltiating activation), and its enediyne warhead positioned to initiate the CalC self sacrifice process.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                              #     ##                          #         ###           
2GKD_A         5 FVRHSVTVKADRKTAFKTFLEGFPEWWPNNfrttk-----vgapLGVDKKG-GRWYEIDe--QGEEHTFGLIRKVDEPDT 76  Micromonospora ...
2GKC_A         5 FVRHSVTVKADRKTAFKTFLEGFPEWWPNNfrttk-----vgapLGVDKKG-GRWYEIDe--QGEEHTFGLIRKVDEPDT 76  Micromonospora ...
YP_002880674 146 PHVHVLRVPTGPQEAFDAFALRLGEWWHPSytads----dtfagVTIEPEVgGAVVEHHa--GGREIPWGTVTTWDPGAE 219 Beutenbergia ca...
ZP_01748894    4 PIKKTLTVPLTAEEAFTLFTTKMDTWWPSAkfsvf----gekakITFPNHKgGDIVETSe--DGQRDVWGTLIAYDPGVF 77  Roseobacter sp....
YP_001535101  19 SLRSSLLVPASVQQAFEVFTGAIADWWVTEytwsgp---gllaaLGMEPWAgGLLYEIGp--HGFRNDWGRVLVWDPPRR 93  Salinispora are...
ZP_01546715    6 ECRVEGILNLPRAQAFSLFVDRLDLWWTSPfknag----dgkveAGIDPYAgGSCYEIDa--GGQHRVWGTVLSLEPPLY 79  Stappia aggrega...
ZP_01741683    4 PVVKTISVPCSQETAFNTFANDLNAWWPKDkhsvsamggeiareVKFDAKQgGEITEVMh--DGTETLWGSAREFSPHSK 81  Rhodobacterales...
YP_001413774   4 AVMVGITLDVEPEEAFRLFTEEVDVWWQRGpkfrfr--prahgtMKFEPGEgGRLVEIYdeaKGDLYEVGRILVWEPGHR 81  Parvibaculum la...
YP_946705     73 PLIITVVVPTNVSHAFQGFTDHPHLWWPLEqesv------fgagSHVEFEE-NLILETAe--DGRTSVWGTIDDWQPPLS 143 Arthrobacter au...
ZP_05113956   20 ECRFESVIPLARLDAFKLVVDHPELWWCPPlseah----sggldVRIEPFAgGACYQIDe--KGQRCIWGTVLSIEEPLY 93  Labrenzia alexa...
Feature 1                 # ### #                                                     ##  #   #  
2GKD_A        77 LVIGWr--lNGFGRIDpd--nsSEFTVTFVADgq---kKTRVDVEHTHFDRmgt-------khaKRVRNGMDKGWPTILQ 142 Micromonospora ...
2GKC_A        77 LVIGWr--lNGFGRIDpd--nsSEFTVTFVADgq---kKTRVDVEHTHFDRmgt-------khaKRVRNGMDKGWPTILQ 142 Micromonospora ...
YP_002880674 220 VAFTFs---LALPEGVs-----SEVRVRFEPApeddgaGTMVRFVHGGWTAe------------NAQYRGKFAEWPVILE 279 Beutenbergia ca...
ZP_01748894   78 LSFTWh---PGRPASEa-----TVVTVEFTQTe----aGTKCDLTHGGFGIlgd--------taDAVSNSYLTGWDLVLG 137 Roseobacter sp....
YP_001535101  94 LVFTWq--iGADRLPVpdparaSEVEALFQPDhs---gRTRVEVEHRHFDRhgr--------aaEGYRRALTTGWSELLA 160 Salinispora are...
ZP_01546715   80 VRLAWqvsrDGEEVPDpa--taSRVMVNFREAg----dSTRLEIVHSEFLRhgea------gaeYLERMRQADGWPRIVD 147 Stappia aggrega...
ZP_01741683   82 LSFAWh---IGKSADEa-----SFVDVTFEAAg----dMTKVTLTHHGWEVfgd--------saAAMREGYNNGWVHVFE 141 Rhodobacterales...
YP_001413774  82 LVFEWr---GPNFREGq----vTEVELKFKAVd----aGTRITLEHRGWETlpqdhparhglsdRAFLTMQGGWWEEQLV 150 Parvibaculum la...
YP_946705    144 FHASWy---PASTPLWs-----TEIRVAFRAVe----eGTEVRLVHDGWEGae---------dpAASRASYAEGWPRVLE 202 Arthrobacter au...
ZP_05113956   94 IRISWq--vAQDGSLIadpaaaSRVMLNFREAg----eVTRVEVVHNKFLRhgea------ggeYMQLMMQSSGWPRILK 161 Labrenzia alexa...
Feature 1         #      
2GKD_A       143 SFQDKIDE 150 Micromonospora echinospora
2GKC_A       143 SFQDKIDE 150 Micromonospora echinospora
YP_002880674 280 RYAALLTP 287 Beutenbergia cavernae DSM 12333
ZP_01748894  138 CYASAVKV 145 Roseobacter sp. CCS2
YP_001535101 161 RYASVVAK 168 Salinispora arenicola CNS-205
ZP_01546715  148 NLKAAARH 155 Stappia aggregata IAM 12614
ZP_01741683  142 TCFAKACG 149 Rhodobacterales bacterium HTCC2150
YP_001413774 151 AMRGKVGR 158 Parvibaculum lavamentivorans DS-1
YP_946705    203 RYVRFMGG 210 Arthrobacter aurescens TC1
ZP_05113956  162 NLVEAAKT 169 Labrenzia alexandrii DFL-11

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