Andrew L. Olson's current address is Department of Structural and Molecular Biology, North Carolina State University, Raleigh, North Carolina, 27695.
Solution structures of Mycobacterium tuberculosis thioredoxin C and models of intact thioredoxin system suggest new approaches to inhibitor and drug design
Article first published online: 15 JAN 2013
Copyright © 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 81, Issue 4, pages 675–689, April 2013
How to Cite
Olson, A. L., Neumann, T. S., Cai, S. and Sem, D. S. (2013), Solution structures of Mycobacterium tuberculosis thioredoxin C and models of intact thioredoxin system suggest new approaches to inhibitor and drug design. Proteins, 81: 675–689. doi: 10.1002/prot.24228
- Issue published online: 8 MAR 2013
- Article first published online: 15 JAN 2013
- Accepted manuscript online: 10 DEC 2012 05:00AM EST
- Manuscript Accepted: 12 NOV 2012
- Manuscript Revised: 26 OCT 2012
- Manuscript Received: 21 AUG 2012
- NIH. Grant Numbers: GM085739, AI101975, S10 RR019012
- NSF CREST. Grant Number: CCLI #1022793
- thioredoxin reductase;
- Mycobacterium tuberculosis;
- solution structure
Here, 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 α4 helix in the previously reported crystal structure, compared with the solution structure. On the basis of 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 2013. © 2012 Wiley Periodicals, Inc.