6bfp: Difference between revisions
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<StructureSection load='6bfp' size='340' side='right'caption='[[6bfp]], [[Resolution|resolution]] 1.29Å' scene=''> | <StructureSection load='6bfp' size='340' side='right'caption='[[6bfp]], [[Resolution|resolution]] 1.29Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6bfp]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6bfp]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=6BFP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DJY:3-{2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethenyl-5-methoxyphenyl}-6-[(cyclopropylmethyl)carbamoyl]pyridine-2-carboxylic+acid'>DJY</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.292Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DJY:3-{2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethenyl-5-methoxyphenyl}-6-[(cyclopropylmethyl)carbamoyl]pyridine-2-carboxylic+acid'>DJY</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bfp OCA], [https://pdbe.org/6bfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bfp RCSB], [https://www.ebi.ac.uk/pdbsum/6bfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bfp ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TRY1_BOVIN TRY1_BOVIN] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6bfp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6bfp" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Trypsin 3D structures|Trypsin 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Choy RM]] | |||
[[Category: Choy | [[Category: Partridge JR]] | ||
[[Category: Partridge | |||
Latest revision as of 17:39, 4 October 2023
Bovine trypsin bound to potent inhibitorBovine trypsin bound to potent inhibitor
Structural highlights
FunctionPublication Abstract from PubMedPlasma 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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