1zgi

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[[Image:1zgi.jpg|left|200px]]
 
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{{Structure
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==thrombin in complex with an oxazolopyridine inhibitor 21==
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|PDB= 1zgi |SIZE=350|CAPTION= <scene name='initialview01'>1zgi</scene>, resolution 2.2&Aring;
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<StructureSection load='1zgi' size='340' side='right'caption='[[1zgi]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=382:(R)-2-(2-(1H-1,2,4-TRIAZOL-1-YL)BENZYL)-N-(2,2-DIFLUORO-2-(PIPERIDIN-2-YL)ETHYL)OXAZOLO[4,5-C]PYRIDIN-4-AMINE'>382</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene>
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<table><tr><td colspan='2'>[[1zgi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZGI FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=382:(R)-2-(2-(1H-1,2,4-TRIAZOL-1-YL)BENZYL)-N-(2,2-DIFLUORO-2-(PIPERIDIN-2-YL)ETHYL)OXAZOLO[4,5-C]PYRIDIN-4-AMINE'>382</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zgi OCA], [https://pdbe.org/1zgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zgi RCSB], [https://www.ebi.ac.uk/pdbsum/1zgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zgi ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zgi OCA], [http://www.ebi.ac.uk/pdbsum/1zgi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zgi RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/HIRV1_HIRME HIRV1_HIRME] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.<ref>PMID:17585879</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zg/1zgi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1zgi ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.
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'''thrombin in complex with an oxazolopyridine inhibitor 21'''
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Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization.,Deng JZ, McMasters DR, Rabbat PM, Williams PD, Coburn CA, Yan Y, Kuo LC, Lewis SD, Lucas BJ, Krueger JA, Strulovici B, Vacca JP, Lyle TA, Burgey CS Bioorg Med Chem Lett. 2005 Oct 15;15(20):4411-6. PMID:16137886<ref>PMID:16137886</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1zgi" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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Thrombin-inhibitor X-ray crystal structures, in combination with the installation of binding elements optimized within the pyrazinone series of thrombin inhibitors, were utilized to transform a weak triazolopyrimidine lead into a series of potent oxazolopyridines. A modification intended to attenuate plasma protein binding (i.e., conversion of the P3 pyridine to a piperidine) conferred significant factor Xa activity to this series. Ultimately, these dual thrombin/factor Xa inhibitors demonstrated excellent in vitro and in vivo anticoagulant efficacy.
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*[[Hirudin 3D structures|Hirudin 3D structures]]
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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==About this Structure==
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== References ==
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1ZGI is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZGI OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Development of an oxazolopyridine series of dual thrombin/factor Xa inhibitors via structure-guided lead optimization., Deng JZ, McMasters DR, Rabbat PM, Williams PD, Coburn CA, Yan Y, Kuo LC, Lewis SD, Lucas BJ, Krueger JA, Strulovici B, Vacca JP, Lyle TA, Burgey CS, Bioorg Med Chem Lett. 2005 Oct 15;15(20):4411-6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16137886 16137886]
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[[Category: Hirudo medicinalis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Thrombin]]
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[[Category: Burgey CS]]
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[[Category: Burgey, C S.]]
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[[Category: Coburn CA]]
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[[Category: Coburn, C A.]]
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[[Category: Deng JZ]]
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[[Category: Deng, J Z.]]
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[[Category: Krueger JA]]
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[[Category: Krueger, J A.]]
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[[Category: Kuo LC]]
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[[Category: Kuo, L C.]]
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[[Category: Lewis SD]]
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[[Category: Lewis, S D.]]
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[[Category: Lucas BJ]]
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[[Category: Lucas, B J.]]
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[[Category: Lyle TA]]
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[[Category: Lyle, T A.]]
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[[Category: McMasters DR]]
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[[Category: McMasters, D R.]]
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[[Category: Rabbat PM]]
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[[Category: Rabbat, P M.]]
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[[Category: Strulovici B]]
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[[Category: Strulovici, B.]]
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[[Category: Vacca JP]]
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[[Category: Vacca, J P.]]
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[[Category: Williams PD]]
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[[Category: Williams, P D.]]
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[[Category: Yan Y]]
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[[Category: Yan, Y.]]
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[[Category: thrombin]]
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[[Category: thrombin inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:35:54 2008''
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Current revision

thrombin in complex with an oxazolopyridine inhibitor 21

PDB ID 1zgi

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