1ilw: Difference between revisions
New page: left|200px<br /><applet load="1ilw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ilw, resolution 2.05Å" /> '''Crystal Structure of... |
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caption="1ilw, resolution 2.05Å" /> | caption="1ilw, resolution 2.05Å" /> | ||
'''Crystal Structure of Pyrazinamidase/Nicotinamidase of Pyrococcus horikoshii'''<br /> | '''Crystal Structure of Pyrazinamidase/Nicotinamidase of Pyrococcus horikoshii'''<br /> | ||
==Overview== | ==Overview== | ||
Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide | 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== | ==About this Structure== | ||
1ILW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Active as [http://en.wikipedia.org/wiki/Nicotinamidase Nicotinamidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.19 3.5.1.19] Full crystallographic information is available from [http:// | 1ILW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Active as [http://en.wikipedia.org/wiki/Nicotinamidase Nicotinamidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.19 3.5.1.19] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ILW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Pyrococcus horikoshii]] | [[Category: Pyrococcus horikoshii]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: BSGC, Berkeley | [[Category: BSGC, Berkeley Structural Genomics Center.]] | ||
[[Category: Du, X.]] | [[Category: Du, X.]] | ||
[[Category: Kim, S | [[Category: Kim, S H.]] | ||
[[Category: amidase]] | [[Category: amidase]] | ||
[[Category: berkeley structural genomics center]] | [[Category: berkeley structural genomics center]] | ||
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[[Category: tuberculosis]] | [[Category: tuberculosis]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:13:12 2008'' | ||
Revision as of 11:13, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 13:13:12 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Nicotinamidase
- Pyrococcus horikoshii
- Single protein
- BSGC, Berkeley Structural Genomics Center.
- Du, X.
- Kim, S H.
- Amidase
- Berkeley structural genomics center
- Bsgc structure funded by nih
- Cysteine hydrolase
- Hydrolase
- Protein structure initiative
- Psi
- Pyrazinamidase
- Pyrazinamide
- Structural genomics
- Tuberculosis
