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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1req

E.C. namemethylmalonyl-CoA mutase
SpeciesPropionibacterium freudenreichii ()
E.C. Number (IntEnz) 5.4.99.2
CSA Homologues of 1req1e1c,1se5,2req,3bic,3req,4req,5req,6req,7req,
CSA Entries With UniProtID P11652
CSA Entries With EC Number 5.4.99.2
PDBe Entry 1req
PDBSum Entry 1req
MACiE Entry M0062

Literature Report

IntroductionIsomerising two important metabolites gives this enzyme significance in the degradation of some amino acids and odd-chain fatty acids, as well as (in bacteria) the biosynthesis of propionate. Like several other mutases, it uses adenosylcobalamin (Vitamin B12) to produce the free radicals essential for the rearrangement, and its sequence is rather well conserved between prokaryotes and eukaryotes.
MechansimThe protein can assist in catalysis in two ways; firstly by encouraging the homolytic cleavage of the Co-C bond in the cofactor, and then during the rearrangement itself. In the first of these two considerations, the axial ligand His610 is clearly important - the 2.5 A bond it forms to Co encourages formation of the active Co(II) species. To maintain this bond length, Asp608 forms a strong H-bond to His610, but this will induce a negative charge on the His, strengthening the Co-C bond. This undesired side-effect is compensated for by Lys604, which is positively charged and bonds to the other side of Asp608. In addition to this triad of residues, several are involved in the rearrangement, although a detailed catalytic mechanism has not yet been elucidated. Arg207 seems to be important in holding the carboxyl group of the substrate in the correct position for catalysis. His244 stabilises the intermediate, as shown by mutagenesis. Mutagenesis also demonstrates that changing Tyr89 to Phe slows both the homolysis of the Co-C bond and the rearrangement itself.
Reaction

Catalytic Sites for 1req

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA608608macie:sideChain
LysA604604macie:sideChain
TyrA8989macie:sideChain
HisA244244macie:sideChain
HisA610610macie:sideChain

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspC608608macie:sideChain
LysC604604macie:sideChain
TyrC8989macie:sideChain
HisC244244macie:sideChain
HisC610610macie:sideChain

Literature References

Notes:
Smith DM.
Understanding the mechanism of B(12)-dependent diol dehydratase: a synergistic retro-push--pull proposal
J Am Chem Soc 2001 123 1664-1675
PubMed: 11456766
Mancia F
How coenzyme B12 radicals are generated: the crystal structure of methylmalonyl-coenzyme A mutase at 2 A resolution.
Structure 1996 4 339-350
PubMed: 8805541
Mancia F
Crystal structure of substrate complexes of methylmalonyl-CoA mutase.
Biochemistry 1999 38 7999-8005
PubMed: 10387043
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