2b7d: Difference between revisions

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-{{Seed}}
-[[Image:2b7d.png|left|200px]]
-<!--
+==Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model==
-The line below this paragraph, containing "STRUCTURE_2b7d", creates the "Structure Box" on the page.
+<StructureSection load='2b7d' size='340' side='right'caption='[[2b7d]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2b7d]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B7D FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1B:(2R)-2-[5-(5-CARBAMIMIDOYL-1H-BENZOIMIDAZOL-2-YL)-6,2-DIHYDROXY-5-UREIDOMETHYL-BIPHENYL-3-YL]-SUCCINIC+ACID'>C1B</scene></td></tr>
-{{STRUCTURE_2b7d|  PDB=2b7d  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2b7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b7d OCA], [https://pdbe.org/2b7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b7d RCSB], [https://www.ebi.ac.uk/pdbsum/2b7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b7d ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[https://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>
+== Function ==
+[https://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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b7/2b7d_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2b7d ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.
-===Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model===
+Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.,Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:16412633<ref>PMID:16412633</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2b7d" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16412633}}, adds the Publication Abstract to the page
+*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 16412633 is the PubMed ID number.
+*[[Tissue factor|Tissue factor]]
--->
+== References ==
-{{ABSTRACT_PUBMED_16412633}}
+<references/>
+__TOC__
-==Disease==
+</StructureSection>
-Known disease associated with this structure: Factor VII deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]], Myocardial infarction, decreased susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]]
-==About this Structure==
-B7D 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=2B7D OCA].
-==Reference==
-Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model., Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR, Bioorg Med Chem Lett. 2006 Apr 1;16(7):2037-41. Epub 2006 Jan 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16412633 16412633]
-[[Category: Coagulation factor VIIa]]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Elrod, K C.]]
+[[Category: Elrod KC]]
-[[Category: Green, M J.]]
+[[Category: Green MJ]]
-[[Category: Hanson, S R.]]
+[[Category: Hanson SR]]
-[[Category: Hu, H.]]
+[[Category: Hu H]]
-[[Category: Janc, J W.]]
+[[Category: Janc JW]]
-[[Category: Katz, B A.]]
+[[Category: Katz BA]]
-[[Category: Kolesnikov, A.]]
+[[Category: Kolesnikov A]]
-[[Category: Leahy, E M.]]
+[[Category: Leahy EM]]
-[[Category: Liu, L.]]
+[[Category: Liu L]]
-[[Category: Marzec, U M.]]
+[[Category: Marzec UM]]
-[[Category: Mordenti, J.]]
+[[Category: Mordenti J]]
-[[Category: Rai, R.]]
+[[Category: Rai R]]
-[[Category: Shrader, W D.]]
+[[Category: Shrader WD]]
-[[Category: Sprengeler, P A.]]
+[[Category: Sprengeler PA]]
-[[Category: Torkelson, S.]]
+[[Category: Torkelson S]]
-[[Category: Young, W B.]]
+[[Category: Young WB]]
-[[Category: Yu, C.]]
+[[Category: Yu C]]
-[[Category: Short hydrogen bond]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 01:58:28 2008''