1o5e: Difference between revisions

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-{{Seed}}
-[[Image:1o5e.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_1o5e", creates the "Structure Box" on the page.
+<StructureSection load='1o5e' size='340' side='right'caption='[[1o5e]], [[Resolution|resolution]] 1.75&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'>[[1o5e]] is a 2 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=1O5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O5E 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]] 1.75&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=132:6-CHLORO-2-(2-HYDROXY-BIPHENYL-3-YL)-1H-INDOLE-5-CARBOXAMIDINE'>132</scene></td></tr>
-{{STRUCTURE_1o5e|  PDB=1o5e  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1o5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o5e OCA], [https://pdbe.org/1o5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o5e RCSB], [https://www.ebi.ac.uk/pdbsum/1o5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o5e ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HEPS_HUMAN HEPS_HUMAN] Plays an essential role in cell growth and maintenance of cell morphology. May mediate the activating cleavage of HGF and MST1/HGFL.<ref>PMID:21875933</ref> <ref>PMID:15839837</ref>
+== 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/o5/1o5e_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1o5e 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>
-The line below this paragraph, {{ABSTRACT_PUBMED_15522303}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 1o5e" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 15522303 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15522303}}
+__TOC__
+</StructureSection>
-==About this Structure==
-O5E 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=1O5E OCA].
-==Reference==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/15522303 15522303]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Chan, H.]]
+[[Category: Chan H]]
-[[Category: Gjerstad, E.]]
+[[Category: Gjerstad E]]
-[[Category: Ho, J D.]]
+[[Category: Ho JD]]
-[[Category: Janc, J W.]]
+[[Category: Janc JW]]
-[[Category: Katz, B A.]]
+[[Category: Katz BA]]
-[[Category: Luong, C.]]
+[[Category: Luong C]]
-[[Category: Mackman, R L.]]
+[[Category: Mackman RL]]
-[[Category: McGrath, M E.]]
+[[Category: McGrath ME]]
-[[Category: Mortara, K.]]
+[[Category: Mortara K]]
-[[Category: Somoza, J R.]]
+[[Category: Somoza JR]]
-[[Category: Sprengeler, P A.]]
+[[Category: Sprengeler PA]]
-[[Category: Tang, J.]]
+[[Category: Tang J]]
-[[Category: Verner, E.]]
+[[Category: Verner E]]
-[[Category: Williams, S R.]]
+[[Category: Williams SR]]
-[[Category: Young, W B.]]
+[[Category: Young WB]]
-[[Category: Conserved water displacement hydrogen bond deficit]]
-[[Category: Factor viia]]
-[[Category: Hepsin]]
-[[Category: S1 site]]
-[[Category: Scavenger receptor cysteine-rich domain]]
-[[Category: Selectivity]]
-[[Category: Serine protease ala190 upa]]
-[[Category: Srcr]]
-[[Category: Thrombin]]
-[[Category: Trypsin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:01:42 2008''