1im5: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1im5.jpg|left|200px]] | [[Image:1im5.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1im5", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1im5| PDB=1im5 | SCENE= }} | ||
}} | |||
'''Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc''' | '''Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc''' | ||
| Line 28: | Line 25: | ||
[[Category: Du, X.]] | [[Category: Du, X.]] | ||
[[Category: Kim, S H.]] | [[Category: Kim, S H.]] | ||
[[Category: | [[Category: Amidase]] | ||
[[Category: | [[Category: Covalent catalysis]] | ||
[[Category: | [[Category: Cysteine hydrolase]] | ||
[[Category: | [[Category: Drug resistance]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Metal ion catalysis]] | ||
[[Category: | [[Category: Nicotinamidase]] | ||
[[Category: | [[Category: Pyrazinamidase]] | ||
[[Category: | [[Category: Pyrazinamide]] | ||
[[Category: | [[Category: Pza resistance]] | ||
[[Category: | [[Category: Tuberculosis]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:08:58 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 17:08, 2 May 2008
Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc
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
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 Page seeded by OCA on Fri May 2 20:08:58 2008
