Download MendeleyA Mycobacterium tuberculosis ligand-binding Mn/Fe protein reveals a new cofactor in a remodeled R2-protein scaffold
Andersson, C.S.(2009) Proc Natl Acad Sci U S A 106: 5633-5638
- PubMed: 19321420
- DOI: https://doi.org/10.1073/pnas.0812971106
- Primary Citation of Related Structures:
3EE4 - PubMed Abstract:
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.
Organizational Affiliation:
Stockholm Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, Arrhenius Laboratories for Natural Sciences C4, SE-106 91 Stockholm, Sweden.
