1o5d: Difference between revisions

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-{{Seed}}
-[[Image:1o5d.png|left|200px]]
-<!--
+==Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)==
-The line below this paragraph, containing "STRUCTURE_1o5d", creates the "Structure Box" on the page.
+<StructureSection load='1o5d' size='340' side='right'caption='[[1o5d]], [[Resolution|resolution]] 2.05&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'>[[1o5d]] 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=1O5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O5D 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]] 2.05&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CR9:2-{5-[AMINO(IMINIO)METHYL]-6-FLUORO-1H-BENZIMIDAZOL-2-YL}-6-[(2-METHYLCYCLOHEXYL)OXY]BENZENOLATE'>CR9</scene></td></tr>
-{{STRUCTURE_1o5d|  PDB=1o5d  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1o5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o5d OCA], [https://pdbe.org/1o5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o5d RCSB], [https://www.ebi.ac.uk/pdbsum/1o5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o5d 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/o5/1o5d_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=1o5d ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A site-directed mutant of the serine protease urokinase-type plasminogen activator (uPA), was produced to assess the contribution of the Ser190 side-chain to the affinity and selectivity of lead uPA inhibitors in the absence of other differences present in comparisons of natural proteases. Crystallography and enzymology involving WT and Ala190 uPA were used to calculate free energy binding contributions of hydrogen bonds involving the Ser190 hydroxyl group (O(gamma)(Ser190)) responsible for the remarkable selectivity of 6-halo-5-amidinoindole and 6-halo-5-amidinobenzimidazole inhibitors toward uPA and against natural Ala190 protease anti-targets. Crystal structures of uPA complexes of novel, active site-directed arylguanidine and 2-aminobenzimidazole inhibitors of WT uPA, together with associated K(i) values for WT and Ala190 uPA, also indicate a significant role of Ser190 in the binding of these classes of uPA inhibitors. Structures and associated K(i) values for a lead inhibitor (CA-11) bound to uPA and to five other proteases, as well as for other leads bound to multiple proteases, help reveal the features responsible for the potency (K(i)=11nM) and selectivity of the remarkably small inhibitor, CA-11. The 6-fluoro-5-amidinobenzimidzole, CA-11, is more than 1000-fold selective against natural Ala190 protease anti-targets, and more than 100-fold selective against other Ser190 anti-targets.
-===Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)===
+Dissecting and designing inhibitor selectivity determinants at the S1 site using an artificial Ala190 protease (Ala190 uPA).,Katz BA, Luong C, Ho JD, Somoza JR, Gjerstad E, Tang J, Williams SR, Verner E, Mackman RL, Young WB, Sprengeler PA, Chan H, Mortara K, Janc JW, McGrath ME J Mol Biol. 2004 Nov 19;344(2):527-47. PMID:15522303<ref>PMID:15522303</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1o5d" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15522303}}, adds the Publication Abstract to the page
+*[[Tissue factor|Tissue factor]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15522303 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15522303}}
+__TOC__
+</StructureSection>
-==Disease==
-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==
-O5D is a 3 chains 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=1O5D OCA].
-==Reference==
-<ref group="xtra">PMID:15522303</ref><references group="xtra"/>
-[[Category: Coagulation factor VIIa]]
 [[Category: Homo sapiens]]
-[[Category: Chan, H.]]
+[[Category: Large Structures]]
-[[Category: Gjerstad, E.]]
+[[Category: Chan H]]
-[[Category: Ho, J D.]]
+[[Category: Gjerstad E]]
-[[Category: Janc, J W.]]
+[[Category: Ho JD]]
-[[Category: Katz, B A.]]
+[[Category: Janc JW]]
-[[Category: Luong, C.]]
+[[Category: Katz BA]]
-[[Category: Mackman, R L.]]
+[[Category: Luong C]]
-[[Category: McGrath, M E.]]
+[[Category: Mackman RL]]
-[[Category: Mortara, K.]]
+[[Category: McGrath ME]]
-[[Category: Somoza, J R.]]
+[[Category: Mortara K]]
-[[Category: Sprengeler, P A.]]
+[[Category: Somoza JR]]
-[[Category: Tang, J.]]
+[[Category: Sprengeler PA]]
-[[Category: Verner, E.]]
+[[Category: Tang J]]
-[[Category: Williams, S R.]]
+[[Category: Verner E]]
-[[Category: Young, W B.]]
+[[Category: Williams SR]]
-[[Category: Ala190 upa]]
+[[Category: Young WB]]
-[[Category: Conserved water displacement hydrogen bond deficit]]
-[[Category: Factor viia]]
-[[Category: Hepsin]]
-[[Category: S1 site]]
-[[Category: Selectivity]]
-[[Category: Thrombin]]
-[[Category: Trypsin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 16:22:40 2009''