title: Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B12Enzyme IcmF.
abstract: IcmF is a 5'-deoxyadenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the carbon skeleton rearrangement of isobutyryl-CoA to butyryl-CoA. It is a bifunctional protein resulting from the fusion of a G-protein chaperone with GTPase activity and the cofactor- and substrate-binding mutase domains with isomerase activity. IcmF is prone to inactivation during catalytic turnover, thus setting up its dependence on a cofactor repair system. Herein, we demonstrate that 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. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system.
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600 and.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600 and.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kitanishi
authors.affiliation: the Department of Physics, Emory University, Atlanta, Georgia 30322-2430.
authors.forename: Umar T
authors.initials: UT
authors.lastname: Twahir
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600 and.
authors.forename: Valentin
authors.initials: V
authors.lastname: Cracan
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600 and.
authors.forename: Derrell
authors.initials: D
authors.lastname: Chapman
authors.affiliation: the Department of Physics, Emory University, Atlanta, Georgia 30322-2430.
authors.forename: Kurt
authors.initials: K
authors.lastname: Warncke
authors.affiliation: From the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0600 and rbanerje@umich.edu.
authors.forename: Ruma
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D056511:Metallochaperones / Q000378:metabolism*; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism; D000072417:Protein Domains; D014166:Transferases / Q000378:metabolism; D014805:Vitamin B 12 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D056511:Metallochaperones; D018832:Molecular Chaperones; C050106:isobutyryl-coenzyme A; C024343:butyryl-coenzyme A; D014166:Transferases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12
keywords: ATP; GTPase; adenosylcobalamin (AdoCbl); low molecular weight G-protein; metalloprotein