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Journal of Bacteriology, July 2003, p. 4110-4118, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4110-4118.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Structure of a Coenzyme A Pyrophosphatase from Deinococcus radiodurans: a Member of the Nudix Family

Lin-Woo Kang,1 Sandra B. Gabelli,1 Mario A. Bianchet,1 Wen Lian Xu,2 Maurice J. Bessman,2 and L. Mario Amzel1*

Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,1 Department of Biology and McCollum-Pratt Institute, Johns Hopkins University, Baltimore, Maryland 212182

Received 4 February 2003/ Accepted 28 April 2003

Gene Dr1184 from Deinococcus radiodurans codes for a Nudix enzyme (DR-CoAse) that hydrolyzes the pyrophosphate moiety of coenzyme A (CoA). Nudix enzymes with the same specificity have been found in yeast, humans, and mice. The three-dimensional structure of DR-CoAse, the first of a Nudix hydrolase with this specificity, reveals that this enzyme contains, in addition to the fold observed in other Nudix enzymes, insertions that are characteristic of a CoA-hydrolyzing Nudix subfamily. The structure of the complex of the enzyme with Mg2+, its activating cation, reveals the position of the catalytic site. A helix, part of the N-terminal insertion, partially occludes the binding site and has to change its position to permit substrate binding. Comparison of the structure of DR-CoAse to those of other Nudix enzymes, together with the location in the structure of the sequence characteristic of CoAses, suggests a mode of binding of the substrate to the enzyme that is compatible with all available data.


* Corresponding author. Mailing address: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205. Phone: (410) 955-3955. Fax: (410) 955-0637. E-mail: mario{at}neruda.med.jhmi.edu.


Journal of Bacteriology, July 2003, p. 4110-4118, Vol. 185, No. 14
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.14.4110-4118.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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