Structure and mechanism of MT-ADPRase, a Nudix hydrolase from Mycobacterium tuberculosis

Lin Woo Kang, Sandra B. Gabelli, Jennifer E. Cunningham, Suzanne F. O'Handley, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Nudix hydrolases are a family of proteins that contain the characteristic sequence GX5EX7REUXEEXG(I/L/V), the Nudix box. They catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives such as ADP-ribose, ApnA (3 ≤ n ≤ 6), NADH, and dATP. A number of Nudix hydrolases from several species, ranging from bacteria to humans, have been characterized, including, in some cases, the determination of their three-dimensional structures. The product of the Rv1700 gene of M. tuberculosis is a Nudix hydrolase specific for ADP-ribose (ADPR). We have determined the crystal structures of MT-ADPRase alone, and in complex with substrate, with substrate and the nonactivating metal ion Gd3+, and in complex with a nonhydrolyzable ADPR analog and the activating metal ion Mn2+. These structures, refined with data extending to resolutions between 2.0 and 2.3 Å, showed that there are sequence differences in binding site residues between MT-ADPRase and a human homolog that may be exploited for antituberculosis drug development.

Original languageEnglish (US)
Pages (from-to)1015-1023
Number of pages9
Issue number8
StatePublished - Aug 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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