Journal Article

PUBDB-2017-03170

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Divergent assembly mechanisms of the manganese/iron cofactors in R2lox and R2c proteins

Kutin, Y. ; Srinivas, V. ; Fritz, M. ; Kositzki, R. ; Shafaat, H. S. ; Birrell, J. ; Bill, E. ; Haumann, M.Extern* ; Lubitz, W. ; Högbom, M. (Corresponding author)Extern* ; Griese, J. J. (Corresponding author)Extern* ; Cox, N. (Corresponding author)

2016
Elsevier New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jinorgbio.2016.04.019

Abstract: 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 Mn(II) and Fe(II) in vitro and catalyzes formation of a tyrosine-valine ether cross-link in the protein scaffold (Griese, J. J., Roos, K., Cox, N., Shafaat, H. S., Branca, R. M., Lehtiö, J., Gräslund, A., Lubitz, W., Siegbahn, P. E., and Högbom, M. (2013) Proc. Natl. Acad. Sci. U.S.A. 110, 17189-17194). Here, we present a detailed structural analysis of R2lox in the nonactivated, reduced, and oxidized resting Mn/Fe- and Fe/Fe-bound states, as well as the nonactivated 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 cross-link, 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 similar mechanisms at the Mn/Fe and Fe/Fe center and that R2lox proteins might utilize either cofactor in vivo based on metal availability.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (POF3-622) (POF3-622)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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