dc.contributor.author | Kang, L. | en_US |
dc.contributor.author | Gabelli, S. | en_US |
dc.contributor.author | Cunningham, J. | en_US |
dc.contributor.author | O'Handley, Suzanne | en_US |
dc.contributor.author | Amzel, L. | en_US |
dc.date.accessioned | 2006-07-19T19:51:50Z | en_US |
dc.date.available | 2006-07-19T19:51:50Z | en_US |
dc.date.issued | 2003-08 | en_US |
dc.identifier.citation | Structure 11N8 (2003) 1015-1023 | en_US |
dc.identifier.issn | 0969-2126 | en_US |
dc.identifier.uri | http://hdl.handle.net/1850/2204 | en_US |
dc.description.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. | en_US |
dc.description.sponsorship | This work was supported by NIH grants AI49485 and GM066895, grant J-497 from the Jeffress Trust Foundation, and a Cottrell College Science Award (CC5180) from Research Corporation. | en_US |
dc.format.extent | 37365 bytes | en_US |
dc.format.mimetype | application/pdf | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier: Structure | en_US |
dc.subject | Hydrolases | en_US |
dc.subject | Nudix | en_US |
dc.subject | Structure | en_US |
dc.subject | Tuberculosis | en_US |
dc.title | Structure and mechanism of MT-ADPRase, a nudix hydrolase from Mycobacterium tuberculosis | en_US |
dc.type | Abstract | en_US |
dc.identifier.url | http://dx.doi.org/10.1016/S0969-2126(03)00154-0 | |