EC Number   |
Cofactor |
Reference |
|---|
   5.4.99.13 | 5'-deoxyadenosylcobalamin |
AdoCbl, required, affinity for AdoCbl is unaffected by the presence of GDP |
748223 |
| 5.4.99.13 | 5'-deoxyadenosylcobalamin |
AdoCbl, required, the active sites in the CmIcmF dimer exhibit identical affinity for AdoCbl. Addition of isovaleryl-CoA to wild-type holo-IcmF results in formation of the intermediate cob(II)alamin. AdoCbl is quantitatively converted to cob(II)alamin when isovaleryl-CoA is added to F598A or to the F598I/L or Q742A mutants inactivating the enzyme. Cob(II)alamin formation in activates the enzyme |
748193 |
| 5.4.99.13 | 5'-deoxyadenosylcobalamin |
AdoCbl, required, two conformations: C3'-endo and C2'-endo, conformational change of the 5'-deoxyadenosyl group from C2'-endo to C3'-endo contributes to initiation of catalysis. Adenosylcobalamin (coenzyme B12) is an organometallic enzyme cofactor for radical chemistry. Its reactivity is based on a unique covalent cobalt-carbon (Co-C) bond that is sufficiently weak to allow for reversible homolytic cleavage in enzyme active sites, generating a 5'-deoxyadenosyl radical in the presence of an appropriate substrate. The radical can then abstract a substrate hydrogen atom and initiate difficult chemical transformations |
748200 |
| 5.4.99.13 | ATP |
- |
677666 |
| 5.4.99.13 | Cobalamin |
- |
677666 |
| 5.4.99.13 | coenzyme A |
- |
677666 |
| 5.4.99.13 | more |
the GTPase activity of IcmF powers the ejection of the inactive cob(II)alamin cofactor and requires the presence of an acceptor protein, adenosyltransferase, for receiving it. Adenosyltransferase in turn converts cob(II)alamin to AdoCbl in the presence of ATP and a reductant. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step. Transfer of inactive cob(II)alamin from ATR to IcmF is disfavored. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the homologous methylmalonyl-CoA mutase/G-protein chaperone system. The nonhydrolyzable analogue, GMPPCP, weakens the affinity of IcmF for AdoCbl by about 60fold and allows loading of only one of two cofactor-binding sites. AdoCbl binding in the presence of GMPPCP is primarily enthalpically driven. The slight inhibition of AdoCbl transfer in the presence of GTP or GDP is likely due to the higher affinity of ATR for AdoCbl in the presence of these nucleotides, while ATP enhances the transfer. kinetics, overview |
748223 |
