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| [[Image:1im5.jpg|left|200px]]
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| {{Structure
| | ==Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc== |
| |PDB= 1im5 |SIZE=350|CAPTION= <scene name='initialview01'>1im5</scene>, resolution 1.65Å
| | <StructureSection load='1im5' size='340' side='right'caption='[[1im5]], [[Resolution|resolution]] 1.65Å' scene=''> |
| |SITE=
| | == Structural highlights == |
| |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
| | <table><tr><td colspan='2'>[[1im5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IM5 FirstGlance]. <br> |
| |ACTIVITY= <span class='plainlinks'>[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] </span>
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.65Å</td></tr> |
| |GENE= PH 999 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=53953 Pyrococcus horikoshii])
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| |DOMAIN=
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1im5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1im5 OCA], [https://pdbe.org/1im5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1im5 RCSB], [https://www.ebi.ac.uk/pdbsum/1im5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1im5 ProSAT]</span></td></tr> |
| |RELATEDENTRY=[[1ilw|1ILW]]
| | </table> |
| |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1im5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1im5 OCA], [http://www.ebi.ac.uk/pdbsum/1im5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1im5 RCSB]</span>
| | == Function == |
| }}
| | [https://www.uniprot.org/uniprot/O58727_PYRHO O58727_PYRHO] |
| | | == Evolutionary Conservation == |
| '''Crystal Structure of Pyrazinamidase of Pyrococcus horikoshii in Complex with Zinc'''
| | [[Image:Consurf_key_small.gif|200px|right]] |
| | | Check<jmol> |
| | | <jmolCheckbox> |
| ==Overview== | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/1im5_consurf.spt"</scriptWhenChecked> |
| 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.
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | | <text>to colour the structure by Evolutionary Conservation</text> |
| ==About this Structure== | | </jmolCheckbox> |
| 1IM5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pyrococcus_horikoshii Pyrococcus horikoshii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IM5 OCA].
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1im5 ConSurf]. |
| | | <div style="clear:both"></div> |
| ==Reference== | | __TOC__ |
| 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:[http://www.ncbi.nlm.nih.gov/pubmed/11714269 11714269]
| | </StructureSection> |
| [[Category: Nicotinamidase]] | | [[Category: Large Structures]] |
| [[Category: Pyrococcus horikoshii]] | | [[Category: Pyrococcus horikoshii]] |
| [[Category: Single protein]]
| | [[Category: Du X]] |
| [[Category: Du, X.]] | | [[Category: Kim S-H]] |
| [[Category: Kim, S H.]] | |
| [[Category: amidase]]
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| [[Category: covalent catalysis]]
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| [[Category: cysteine hydrolase]]
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| [[Category: drug resistance]]
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| [[Category: hydrolase]]
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| [[Category: metal ion catalysis]]
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| [[Category: nicotinamidase]]
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| [[Category: pyrazinamidase]]
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| [[Category: pyrazinamide]]
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| [[Category: pza resistance]]
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| [[Category: tuberculosis]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:21:38 2008''
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