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Catalytic Site Atlas

CSA LITERATURE entry for 1ef8

E.C. namemethylmalonyl-CoA decarboxylase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 4.1.1.41
CSA Homologues of 1ef81ef9,
CSA Entries With UniProtID P52045
CSA Entries With EC Number 4.1.1.41
PDBe Entry 1ef8
PDBSum Entry 1ef8
MACiE Entry M0070

Literature Report

IntroductionMethylmalonyl-CoA decarboxylase (MMCD) is a member of the cronotase super family, a collection of enzymes characterised by the presence of oxy anion intermediates or transition states with a significant localisation of negative charge in their reactions. The breadth of catalytic action within this family is demonstrated by the spread of associated enzymes across all six of the Enzyme Commission classes.
MechansimMMCD catalyses the decarboxylation of (S)-methylmalonyl-CoA, forming propionyl-CoA and provides a pathway for the decarboxylation of succinate in E. Coli. The Tyr 140 residue binds to the anionic malonyl substrate through hydrogen bonding, and has been implicated in assisting decarboxylation. The sp2 anionic enolate oxygen points towards an oxyanion hole created by the backbone amide groups of His 66 and Gly110, introducing greater stability to the charged intermediate. The generally non polar nature of the binding pocket surrounding Tyr 140 destabilises the anionic carboxylate group, enhancing the rate of loss of CO2. An unspecified residue acts as a proton donor to the alpha carbon, forming the propionyl-CoA product.
Reaction

Catalytic Sites for 1ef8

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA140140macie:sideChainside chain Function notes: The residue binds the carboxylate group of the substrate and facilitates decarboxylation by orientating the carboxylate group orthogonal to the plane of the thioester carbonyl group through hydrogen bonding.
GlyA110110macie:mainChainAmideThe residue backbone NH forms part of an oxyanion hole, stabilising the enolate anion intermediate.
HisA6666macie:mainChainAmideThe residue backbone NH forms part of an oxyanion hole, stabilising the enolate anion intermediate.

Literature References

Notes:The structural information available at present cannot determine the acidic residue implicated in proton transfer to the enolate intermediate.
Benning MM
New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli.
Biochemistry 2000 39 4630-4639
PubMed: 10769118
Hamed RB
Mechanisms and structures of crotonase superfamily enzymes--how nature controls enolate and oxyanion reactivity.
Cell Mol Life Sci 2008 65 2507-2527
PubMed: 18470480
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