4x8t

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'''Unreleased structure'''
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==FACTOR VIIA IN COMPLEX WITH THE INHIBITOR 7-chloro-3,4-dihydroisoquinolin-1(2H)-one==
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<StructureSection load='4x8t' size='340' side='right' caption='[[4x8t]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4x8t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X8T FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3Z8:7-CHLORO-3,4-DIHYDROISOQUINOLIN-1(2H)-ONE'>3Z8</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x8s|4x8s]], [[4x8u|4x8u]], [[4x8v|4x8v]]</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4x8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x8t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x8t RCSB], [http://www.ebi.ac.uk/pdbsum/4x8t PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN]] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[http://omim.org/entry/227500 227500]]. A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels.<ref>PMID:8043443</ref> <ref>PMID:2070047</ref> <ref>PMID:1634227</ref> <ref>PMID:8364544</ref> <ref>PMID:8204879</ref> <ref>PMID:7981691</ref> <ref>PMID:7974346</ref> <ref>PMID:8652821</ref> <ref>PMID:8844208</ref> <ref>PMID:8940045</ref> <ref>PMID:8883260</ref> <ref>PMID:9414278</ref> <ref>PMID:9576180</ref> <ref>PMID:9452082</ref> <ref>PMID:11091194</ref> <ref>PMID:11129332</ref> <ref>PMID:10862079</ref> <ref>PMID:12472587</ref> <ref>PMID:14717781</ref> <ref>PMID:19751712</ref> <ref>PMID:18976247</ref> <ref>PMID:19432927</ref> <ref>PMID:21206266</ref> <ref>PMID:21372693</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN]] Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A multidisciplinary, fragment-based screening approach involving protein ensemble docking and biochemical and NMR assays is described. This approach led to the discovery of several structurally diverse, neutral surrogates for cationic factor VIIa P1 groups, which are generally associated with poor pharmacokinetic (PK) properties. Among the novel factor VIIa inhibitory fragments identified were aryl halides, lactams, and heterocycles. Crystallographic structures for several bound fragments were obtained, leading to the successful design of a potent factor VIIa inhibitor with a neutral lactam P1 and improved permeability.
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The entry 4x8t is ON HOLD until Paper Publication
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Discovery of Novel P1 Groups for Coagulation Factor VIIa Inhibition Using Fragment-Based Screening.,Cheney DL, Bozarth JM, Metzler WJ, Morin PE, Mueller L, Newitt JA, Nirschl AH, Rendina AR, Tamura JK, Wei A, Wen X, Wurtz NR, Seiffert DA, Wexler RR, Priestley ES J Med Chem. 2015 Mar 12. PMID:25764119<ref>PMID:25764119</ref>
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Authors: Wei, A.
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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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Description: FACTOR VIIA IN COMPLEX WITH THE INHIBITOR 7-CHLORO-1,2,3,4-TETRAHYDROISOQUINOLIN-1-ONE
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== References ==
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[[Category: Unreleased Structures]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Coagulation factor VIIa]]
[[Category: Wei, A]]
[[Category: Wei, A]]
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[[Category: Blood coagulation factor]]
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[[Category: Calcium- binding]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Plasma]]
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[[Category: Protein inhibitor complex]]
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[[Category: Serine protease]]

Revision as of 13:58, 26 March 2015

FACTOR VIIA IN COMPLEX WITH THE INHIBITOR 7-chloro-3,4-dihydroisoquinolin-1(2H)-one

4x8t, resolution 2.20Å

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