2i3a

From Proteopedia

proteopedia linkproteopedia link

spinqualitylabelsall models 2i3a, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of N-Acetyl-gamma-Glutamyl-Phosphate Reductase (Rv1652) from Mycobacterium tuberculosis

Overview

The enzyme N-acetyl-gamma-glutamyl-phosphate reductase (AGPR) catalyzes, the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent, reductive dephosphorylation of N-acetyl-gamma-glutamyl-phosphate to, N-acetylglutamate-gamma-semialdehyde. This reaction is part of the, arginine biosynthetic pathway that is essential for some microorganisms, and plants, in particular, for Mycobacterium tuberculosis (Mtb). The, structures of apo MtbAGPR in the space groups P2(1)2(1)2(1) and C2 and the, structure of MtbAGPR bound to the cofactor NADP(+) have been solved and, analyzed. Each MtbAGPR subunit consists of alpha/beta and alpha+beta, domains; NADP(+) is bound in the cleft between them. The hydrogen bonds, and hydrophobic contacts between the enzyme and cofactor have been, examined. Comparison of the apo and the bound enzyme structures has, revealed a conformational change in MtbAGPR upon NADP(+) binding. Namely, a loop (Leu88 to His92) moves more than 5 A to confine sterically the, cofactor's adenine moiety in a hydrophobic pocket. To identify the, catalytically important residues in MtbAGPR, a docking of the substrate to, the enzyme has been performed using the present structure of the, MtbAGPR/NADP(+) complex. It reveals that residues His217 and His219 could, form hydrogen bonds with the docked substrate. In addition, an ion pair, could form between the substrate phosphate group and the guanidinium group, of Arg114. These interactions optimally place and orient the substrate for, subsequent nucleophilic attack by Cys158 on the substrate gamma-carboxyl, group. His219 is the most probable general base to accept a proton from, Cys158 and an adjacent ion pair interaction with the side-chain carboxyl, group of Glu222 could help to stabilize the resulting positive charge on, His219. For this catalytic triad to function efficiently it requires a, small conformational change of the order of 1 A in the loop containing, His217 and His219; this could easily result from the substrate binding.

About this Structure

2I3A is a Single protein structure of sequence from Mycobacterium tuberculosis with BTB as ligand. Active as N-acetyl-gamma-glutamyl-phosphate reductase, with EC number 1.2.1.38 Full crystallographic information is available from OCA.

Reference

Crystal Structure of N-acetyl-gamma-glutamyl-phosphate Reductase from Mycobacterium tuberculosis in Complex with NADP(+)., Cherney LT, Cherney MM, Garen CR, Niu C, Moradian F, James MN, J Mol Biol. 2007 Apr 13;367(5):1357-69. Epub 2007 Jan 20. PMID:17316682

Page seeded by OCA on Wed Nov 21 12:08:15 2007