6bfp: Difference between revisions

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 ==Bovine trypsin bound to potent inhibitor==
-<StructureSection load='6bfp' size='340' side='right' caption='[[6bfp]], [[Resolution|resolution]] 1.29&Aring;' scene=''>
+<StructureSection load='6bfp' size='340' side='right'caption='[[6bfp]], [[Resolution|resolution]] 1.29&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6bfp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BFP FirstGlance]. <br>
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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=6bfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bfp OCA], [http://pdbe.org/6bfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bfp RCSB], [http://www.ebi.ac.uk/pdbsum/6bfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bfp ProSAT]</span></td></tr>
 </table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Plasma kallikrein (pKal) is a serine protease responsible for cleaving high-molecular-weight kininogen to produce the pro-inflammatory peptide, bradykinin. Unregulated pKal activity can lead to hereditary angioedema (HAE) following excess bradykinin release. HAE attacks can lead to a compromised airway that can be life threatening. As there are limited agents for prophylaxis of HAE attacks, there is a high unmet need for a therapeutic agent for regulating pKal with a high degree of specificity. Here we present crystal structures of both full-length and the protease domain of pKal, bound to two very distinct classes of small-molecule inhibitors: compound 1, and BCX4161. Both inhibitors demonstrate low nM inhibitory potency for pKal and varying specificity for related serine proteases. Compound 1 utilizes a surprising mode of interaction and upon binding results in a rearrangement of the binding pocket. Co-crystal structures of pKal describes why this class of small-molecule inhibitor is potent. Lack of conservation in surrounding residues explains the approximately 10,000-fold specificity over structurally similar proteases, as shown by in vitro protease inhibition data. Structural information, combined with biochemical and enzymatic analyses, provides a novel scaffold for the design of targeted oral small molecule inhibitors of pKal for treatment of HAE and other diseases resulting from unregulated plasma kallikrein activity.
+Structures of full-length plasma kallikrein bound to highly specific inhibitors describe a new mode of targeted inhibition.,Partridge JR, Choy RM, Silva-Garcia A, Yu C, Li Z, Sham H, Metcalf B J Struct Biol. 2019 Mar 12. pii: S1047-8477(19)30046-2. doi:, 10.1016/j.jsb.2019.03.001. PMID:30876891<ref>PMID:30876891</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6bfp" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
 [[Category: Bos taurus]]
+[[Category: Large Structures]]
 [[Category: Trypsin]]
 [[Category: Choy, R M]]