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Solution Structures of Oxidized and Reduced Thioredoxin C from M. tb
Structural highlights
FunctionTHIO_MYCTU Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (By similarity). Publication Abstract from PubMedHere we report the NMR solution structures of Mycobacterium tuberculosis (M. tuberculosis) thioredoxin C in both oxidized and reduced states, with discussion of structural changes that occur in going between redox states. The NMR solution structure of the oxidized TrxC corresponds closely to that of the crystal structure, except in the C-terminal region. It appears that crystal packing effects have caused an artifactual shift in the alpha4 helix in the previously reported crystal structure, compared to the solution structure. Based on these TrxC structures, chemical shift mapping, a previously reported crystal structure of the M. tuberculosis thioredoxin reductase (not bound to a Trx) and structures for intermediates in the E. coli thioredoxin catalytic cycle, we have modeled the complete M. tuberculosis thioredoxin system for the various steps in the catalytic cycle. These structures and models reveal pockets at the TrxR/TrxC interface in various steps in the catalytic cycle, which can be targeted in the design of uncompetitive inhibitors as potential anti-mycobacterial agents, or as chemical genetic probes of function. Proteins 2012. (c) 2012 Wiley Periodicals, Inc. Solution structures of mycobacterium tuberculosis thioredoxin C and models of the intact thioredoxin system suggest new approaches to inhibitor and drug design.,Olson AL, Neumann TS, Cai S, Sem DS Proteins. 2012 Dec 10. doi: 10.1002/prot.24228. PMID:23229911[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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