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Publication Abstract from PubMed

Two recently discovered groups of prokaryotic di-metal carboxylate proteins harbor a heterodinuclear Mn/Fe cofactor. These are the class Ic ribonucleotide reductase R2 proteins and a group of oxidases that are found predominantly in pathogens and extremophiles, called R2-like ligand-binding oxidases (R2lox). We have recently shown that the Mn/Fe cofactor of R2lox self-assembles from MnII and FeII in vitro and catalyzes formation of a tyrosine-valine ether crosslink in the protein scaffold [Griese JJ et al. (2013) Proc. Natl. Acad. Sci. USA 110:17189-17194]. Here we present a detailed structural analysis of R2lox in the non-activated, reduced and oxidized resting Mn/Fe- and Fe/Fe-bound states, as well as the non-activated Mn/Mn-bound state. X-ray crystallography and X-ray absorption spectroscopy demonstrate that the active site ligand configuration of R2lox is essentially the same regardless of cofactor composition. Both the Mn/Fe and the diiron cofactor activate oxygen and catalyze formation of the ether crosslink, whereas the dimanganese cluster does not. The structures delineate likely routes for gated oxygen and substrate access to the active site that are controlled by the redox state of the cofactor. These results suggest that oxygen activation proceeds via the same mechanism at the Mn/Fe and Fe/Fe center, and that R2lox proteins might utilize either cofactor in vivo based on metal availability.

Structural Basis for Oxygen Activation at a Heterodinuclear Mn/Fe Cofactor.,Griese JJ, Kositzki R, Schrapers P, Branca RM, Nordstrom A, Lehtio J, Haumann M, Hogbom M J Biol Chem. 2015 Aug 31. pii: jbc.M115.675223. PMID:26324712^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.