Mobile Loop Dynamics in Adenosyltransferase Control
Mobile loop dynamics in adenosyltransferase control binding and reactivity of coenzyme B12 Romila Mascarenhasa,1, Markus Ruetza,1, Liam McDevitta, Markos Koutmosb,c, and Ruma Banerjeea,2 aDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0600; bDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109-0600, and cDepartment of Biophysics, University of Michigan, Ann Arbor, MI 48109-0600 Edited by Amie K. Boal, Pennsylvania State University, State College, PA, and accepted by Editorial Board Member Stephen J. Benkovic October 20, 2020 (received for review April 16, 2020) Cobalamin is a complex organometallic cofactor that is processed Human and Methylobacterium extorquens (Me) ATR, which have and targeted via a network of chaperones to its dependent been characterized most extensively, also double as chaperones, enzymes. AdoCbl (5′-deoxyadenosylcobalamin) is synthesized transferring AdoCbl directly to MCM (Fig. 1A) rather than re- from cob(II)alamin in a reductive adenosylation reaction catalyzed leasing the high-value product into solution (12–17). Cofactor by adenosyltransferase (ATR), which also serves as an escort, de- loading onto MCM is gated by the GTPase activity of the G livering AdoCbl to methylmalonyl-CoA mutase (MCM). The mech- protein chaperone CblA (18). Despite the overall structural and anism by which ATR signals that its cofactor cargo is ready functional conservation of the cofactor loading processes, there (AdoCbl) or not [cob(II)alamin] for transfer to MCM, is not known. are important differences in regulation between the human (19) In this study, we have obtained crystallographic snapshots that – reveal ligand-induced ordering of the N terminus of Mycobacte- and the better-characterized bacterial systems (15 17).
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