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Catalytic Site Atlas

CSA LITERATURE entry for 1kez

E.C. name6-deoxyerythronolide-B synthase
SpeciesSaccharopolyspora erythraea (strain NRRL 23338)
E.C. Number (IntEnz) 2.3.1.94
CSA Homologues of 1kez1jmk,1mo2,2vsq,
CSA Entries With UniProtID Q03133
CSA Entries With EC Number 2.3.1.94
PDBe Entry 1kez
PDBSum Entry 1kez
MACiE Entry 1kez

Literature Report

IntroductionThioesterase domain of 6-deoxyerythronolide B synthase, a polyketide synthase, catalyses the cyclisation and release of 6-deoxyerythronolide B via lactonisation. 6-deoxyerythronolide B is the macrocyclic core of the antibiotic erythromycin
MechansimThe catalytic triad consists of Asp169, His259 and Ser142. His259, stabilised by Asp-169, acts as a base that deprotonates Ser-142, as it attacks the ACP6-bound thioester substrate, to yield an acyl-O-serine intermediate. The NH of Ala-143 may serve as the oxyanion stabilising residue. The enzyme-bound intermediate is subsequently attacked by a hydroxyl group on the polyketide chain.
Reaction

Catalytic Sites for 1kez

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA1423031macie:sideChainIt nucleophilically attacks the thioester substrate upon deprotonation by His 259.
HisA2593148macie:sideChainIt deprotonates Ser 142 to allow its nucleophilic attack of thioester substrate to yield an acyl-O-serine intermediate.
AlaA1433032macie:mainChainAmideIts backbone NH lines the oxyanion hole and acts as a hydrogen bond donor to the C1 carbonyl
AspA1693058macie:sideChainIt alters the pKa of His 259 and stabilise it for the deprotonation of Ser 142

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerB1423031macie:sideChainIt nucleophilically attacks the thioester substrate upon deprotonation by His 259.
HisB2593148macie:sideChainIt deprotonates Ser 142 to allow its nucleophilic attack of thioester substrate to yield an acyl-O-serine intermediate.
AlaB1433032macie:mainChainAmideIts backbone NH lines the oxyanion hole and acts as a hydrogen bond donor to the C1 carbonyl
AspB1693058macie:sideChainIt alters the pKa of His 259 and stabilise it for the deprotonation of Ser 142

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerC1423031macie:sideChainIt nucleophilically attacks the thioester substrate upon deprotonation by His 259.
HisC2593148macie:sideChainIt deprotonates Ser 142 to allow its nucleophilic attack of thioester substrate to yield an acyl-O-serine intermediate.
AlaC1433032macie:mainChainAmideIts backbone NH lines the oxyanion hole and acts as a hydrogen bond donor to the C1 carbonyl
AspC1693058macie:sideChainIt alters the pKa of His 259 and stabilise it for the deprotonation of Ser 142

Literature References

Notes:
Tsai SC
Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel.
Proc Natl Acad Sci U S A 2001 98 14808-14813
PubMed: 11752428
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