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Journal of Bacteriology, July 2003, p. 4119-4126, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4119-4126.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Structure of Mycobacterium tuberculosis Methionine Sulfoxide Reductase A in Complex with Protein-Bound Methionine

Alexander B. Taylor,1 David M. Benglis, Jr.,2 Subramanian Dhandayuthapani,3 and P. John Hart1*

Department of Biochemistry and the X-Ray Crystallography Core Laboratory,1 School of Medicine,2 Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 782293

Received 13 February 2003/ Accepted 1 May 2003

Peptide methionine sulfoxide reductase (MsrA) repairs oxidative damage to methionine residues arising from reactive oxygen species and reactive nitrogen intermediates. MsrA activity is found in a wide variety of organisms, and it is implicated as one of the primary defenses against oxidative stress. Disruption of the gene encoding MsrA in several pathogenic bacteria responsible for infections in humans results in the loss of their ability to colonize host cells. Here, we present the X-ray crystal structure of MsrA from the pathogenic bacterium Mycobacterium tuberculosis refined to 1.5 Å resolution. In contrast to the three catalytic cysteine residues found in previously characterized MsrA structures, M. tuberculosis MsrA represents a class containing only two functional cysteine residues. The structure reveals a methionine residue of one MsrA molecule bound at the active site of a neighboring molecule in the crystal lattice and thus serves as an excellent model for protein-bound methionine sulfoxide recognition and repair.


* Corresponding author. Mailing address: Department of Biochemistry, X-Ray Crystallography Core Laboratory, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. Phone: (210) 567-0751. Fax: (210) 567-6595. E-mail: pjhart{at}biochem.uthscsa.edu.


Journal of Bacteriology, July 2003, p. 4119-4126, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4119-4126.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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