Mirror "base-off" conformation of coenzyme B12 in human adenosyltransferase and its downstream target, methylmalonyl-CoA mutase.
Human adenosyltransferase synthesizes coenzyme B12, for the target mitochondrial B12 enzyme, methylmalonyl-CoA mutase. It binds B12 in the "base-off" conformation in both the Co2+ and Co3+ oxidation states as revealed by UV-visible and EPR spectroscopy although it lacks the signature DXHXXG motif found in other B12 proteins that bind the cofactor in this conformation. The "base-off" conformation, which is rare at physiological pH, mirrors that in the target enzyme, methylmalonyl-CoA mutase, which utilizes the product, AdoCbl. However, the coordination environment for cobalt in the two proteins is distinct, which is reflected in an approximately 40-fold difference in their affinity for the cofactor.
Yamanishi
Mamoru
M
Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588-0664, USA
Labunska
Tetyana
T
Banerjee
Ruma
R
D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000378:metabolism; D003038:Cobamides / Q000737:chemistry* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D007700:Kinetics; D008765:Methylmalonyl-CoA Mutase / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D003038:Cobamides; C097751:cob(II)alamin; D019883:Alkyl and Aryl Transferases; C019920:cob(I)alamin adenosyltransferase; D008765:Methylmalonyl-CoA Mutase; C000913:cobamamide; D014805:Vitamin B 12