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| {{STRUCTURE_1ilw| PDB=1ilw | SCENE= }} | | {{STRUCTURE_1ilw| PDB=1ilw | SCENE= }} |
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| '''Crystal Structure of Pyrazinamidase/Nicotinamidase of Pyrococcus horikoshii'''
| | ===Crystal Structure of Pyrazinamidase/Nicotinamidase of Pyrococcus horikoshii=== |
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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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11714269}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11714269 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11714269}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Structural genomic]] | | [[Category: Structural genomic]] |
| [[Category: Tuberculosis]] | | [[Category: Tuberculosis]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:08:18 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 13:29:28 2008'' |
