1im5

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{{STRUCTURE_1im5| PDB=1im5 | SCENE= }}
{{STRUCTURE_1im5| PDB=1im5 | SCENE= }}
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'''Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc'''
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===Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_11714269}}
==About this Structure==
==About this Structure==
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[[Category: Pza resistance]]
[[Category: Pza resistance]]
[[Category: Tuberculosis]]
[[Category: Tuberculosis]]
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Revision as of 10:30, 1 July 2008

Image:1im5.png

Template:STRUCTURE 1im5

Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc

Template:ABSTRACT PUBMED 11714269

About this Structure

1IM5 is a Single protein structure of sequence from Pyrococcus horikoshii. 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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