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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1xny

E.C. namepropionyl-CoA carboxylase
SpeciesStreptomyces coelicolor (Bacteria)
E.C. Number (IntEnz) 6.4.1.3
CSA Homologues of 1xnyThere are 25 Homologs
CSA Entries With UniProtID Q9X4K7
CSA Entries With EC Number 6.4.1.3
PDBe Entry 1xny
PDBSum Entry 1xny
MACiE Entry M0201

Literature Report

IntroductionPropionyl-CoA carboxylase (PCC) from Streptomyces coelicolor catalyses the carboxylation of proprionyl-CoA (and, less efficiently, butyryl-CoA) to provide methylmalonyl-CoA (or ethylmalonyl-CoA). This carboxylation reaction provides key extender units for the biosynthesis of fatty acids and polyketide natural products.
PCC has three units, pccA, pccB and pccE. pccA contains the BCCP (biotin carboxyl carrier protein) and BC (biotin carboxylase) domains. The pccB unit contains the carboxyltransferase (CT) function, which transfers the carboxyl group from biotin to propionyl-CoA. pccE may act to associate pccA and pccB.
The pccB unit shows sequence and structure homology with other carboxyltransferases from other organisms. They are all dimers or hexamers, with the monomers comprising two domains; two active sites run between each pair of adjacent monomers, with catalytic residues being contributed from the C-terminal domain from one monomer and the N-terminal domain from the next monomer.
MechansimThe substrate proprionyl-CoA, and cofactor carboxylbiotin (covalently attached to pccA), both have carbonyl groups which hydrogen bond to backbone amides: Gly 182 and Gly 183 for the substrate, Gly 419' and Ala 420' for the carboxylbiotin. (The primed numbers indicate residues on a different monomer to the unprimed residues.) These amides serve as oxyanion holes whenever the need arises.
1) Carboxylbiotin has a pi orbital spanning the CO2-N1-CO-N atoms. Binding to the enzyme bends this orbital (no specific residues indicated) and induces release of CO2. This moves the negative charge of the carboxylate group to the -CO- carbonyl group (to give a ureido enolate), which is stabilised by its oxyanion hole.
2) The ureido enolate collapses, deprotonating propionyl-CoA to give the enolate and regenerating biotin. The substrate enolate is stabilised by its oxyanion hole.
3) The enolate attacks CO2 through the alpha-carbon, reforming the C=O double bond and attaching a carboxyl group to the substrate to give methylmalonate-CoA.
Reaction

Catalytic Sites for 1xny

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA183183macie:mainChainAmideActs as an oxyanion hole for the substrate enolate.
GlyA182182macie:mainChainAmideActs as an oxyanion hole for the substrate enolate.
GlyB419419macie:mainChainAmideActs as an oxyanion hole for the cofactor ureido enolate.
AlaB420420macie:mainChainAmideActs as an oxyanion hole for the cofactor ureido enolate.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA419419macie:mainChainAmideActs as an oxyanion hole for the cofactor ureido enolate.
AlaA420420macie:mainChainAmideActs as an oxyanion hole for the cofactor ureido enolate.
GlyB182182macie:mainChainAmideActs as an oxyanion hole for the substrate enolate.
GlyB183183macie:mainChainAmideActs as an oxyanion hole for the substrate enolate.

Literature References

Notes:Other mechanisms are feasible, but the above mechanism is the most consistent with pH studies and the crystal structure. The literature authors caution that the mechanism suggested is based on the cocrystal structure of biotin with propionyl-CoA, which is not a productive substrate pair.
Diacovich L
Crystal structure of the beta-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity.
Biochemistry 2004 43 14027-14036
PubMed: 15518551
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