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

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Title: Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis
Author: Kang, L.; Gabelli, S.; Cunningham, J.; O'Handley, Suzanne; Amzel, L.
Abstract: Nudix hydrolases are a family of proteins that contain the characteristic sequence GX(5)EX(7)REUXEEXG(I/L/V), the Nudix box. They catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives such as ADP-ribose, Ap(n)A (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 Gd(3+), and in complex with a nonhydrolyzable ADPR analog and the activating metal ion Mn(2+). These structures, refined with data extending to resolutions between 2.0 and 2.3 A, 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.
Record URI: http://hdl.handle.net/1850/2204
Publishers URL: http://dx.doi.org/10.1016/S0969-2126(03)00154-0
Date: 2003-08

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