A Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 1091-6490, Vol. 106, no 14, 5633-8 p.Article in journal (Refereed) Published
Chlamydia trachomatis R2c is the prototype for a recently discovered group of ribonucleotide reductase R2 proteins that use a heterodinuclear Mn/Fe redox cofactor for radical generation and storage. Here, we show that the Mycobacterium tuberculosis protein Rv0233, an R2 homologue and a potential virulence factor, contains the heterodinuclear manganese/iron-carboxylate cofactor but displays a drastic remodeling of the R2 protein scaffold into a ligand-binding oxidase. The first structural characterization of the heterodinuclear cofactor shows that the site is highly specific for manganese and iron in their respective positions despite a symmetric arrangement of coordinating residues. In this protein scaffold, the Mn/Fe cofactor supports potent 2-electron oxidations as revealed by an unprecedented tyrosine-valine crosslink in the active site. This wolf in sheep's clothing defines a distinct functional group among R2 homologues and may represent a structural and functional counterpart of the evolutionary ancestor of R2s and bacterial multicomponent monooxygenases.
Place, publisher, year, edition, pages
2009. Vol. 106, no 14, 5633-8 p.
bioinorganic chemistry, diiron, manganese, monooxygenase, R2c
Research subject Biophysics; Biochemistry
IdentifiersURN: urn:nbn:se:su:diva-32232DOI: 10.1073/pnas.0812971106ISI: 000264967500034PubMedID: 19321420OAI: oai:DiVA.org:su-32232DiVA: diva2:279828