1im5
| |||||||
| , resolution 1.65Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | PH 999 (Pyrococcus horikoshii) | ||||||
| Activity: | Nicotinamidase, with EC number 3.5.1.19 | ||||||
| Related: | 1ILW
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc
OverviewOverview
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 StructureAbout this Structure
1IM5 is a Single protein structure of sequence from Pyrococcus horikoshii. Full crystallographic information is available from OCA.
ReferenceReference
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 Sun Mar 30 21:21:38 2008