1ilw

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Revision as of 20:04, 24 November 2007

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spinqualitylabelsall models 1ilw, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Pyrazinamidase/Nicotinamidase of Pyrococcus horikoshii

Overview

Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide, (PZA) to ammonia and pyrazinoic acid, which is active against, Mycobacterium tuberculosis. Loss of PZAase activity is the major mechanism, of pyrazinamide-resistance by M. tuberculosis. We have determined the, crystal structure of the gene product of Pyrococcus horikoshii 999, (PH999), a PZAase, and its complex with zinc ion by X-ray crystallography., The overall fold of PH999 is similar to that of N-carbamoylsarcosine, amidohydrolase (CSHase) of Arthrobacter sp. and YcaC of Escherichia coli, a protein with unknown physiological function. The active site of PH999, was identified by structural features that are also present in the active, sites of CSHase and YcaC: a triad (D10, K94, and C133) and a cis-peptide, (between V128 and A129). Surprisingly, a metal ion-binding site was, revealed in the active site and subsequently confirmed by crystal, structure of PH999 in complex with Zn(2+). The roles of the triad, cis-peptide, and metal ion in the catalysis are proposed. Because of, extensive homology between PH999 and PZAase of M. tuberculosis (37%, sequence identity), the structure of PH999 provides a structural basis for, understanding PZA-resistance by M. tuberculosis harboring PZAase, mutations.

About this Structure

1ILW is a Single protein structure of sequence from Pyrococcus horikoshii. Active as Nicotinamidase, with EC number 3.5.1.19 Full crystallographic information is available from OCA.

Reference

Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii., Du X, Wang W, Kim R, Yakota H, Nguyen H, Kim SH, Biochemistry. 2001 Nov 27;40(47):14166-72. PMID:11714269

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