5tz9
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of plasma kallikrein protease domain with inhibitor== | |
| + | <StructureSection load='5tz9' size='340' side='right' caption='[[5tz9]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5tz9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TZ9 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7SD:N-[(6-amino-2,4-dimethylpyridin-3-yl)methyl]-1-({4-[(1H-pyrazol-1-yl)methyl]phenyl}methyl)-1H-pyrazole-4-carboxamide'>7SD</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Plasma_kallikrein Plasma kallikrein], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.34 3.4.21.34] </span></td></tr> | ||
| + | <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=5tz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tz9 OCA], [http://pdbe.org/5tz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tz9 RCSB], [http://www.ebi.ac.uk/pdbsum/5tz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tz9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/KLKB1_HUMAN KLKB1_HUMAN]] Defects in KLKB1 are the cause of prekallikrein deficiency (PKK deficiency) [MIM:[http://omim.org/entry/612423 612423]]; also known as Fletcher factor deficiency. This disorder is a blood coagulation defect. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/KLKB1_HUMAN KLKB1_HUMAN]] The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of macrocyclic analogues were designed and synthesized based on the cocrystal structure of small molecule plasma kallikrein (pKal) inhibitor, 2, with the pKal protease domain. This led to the discovery of a potent macrocyclic pKal inhibitor 29, with an IC50 of 2 nM for one olefinic isomer and 42.3 nM for the other olefinic isomer. | ||
| - | + | Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors.,Li Z, Partridge J, Silva-Garcia A, Rademacher P, Betz A, Xu Q, Sham H, Hu Y, Shan Y, Liu B, Zhang Y, Shi H, Xu Q, Ma X, Zhang L ACS Med Chem Lett. 2016 Dec 6;8(2):185-190. doi: 10.1021/acsmedchemlett.6b00384. , eCollection 2017 Feb 9. PMID:28197309<ref>PMID:28197309</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5tz9" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Plasma kallikrein]] | ||
[[Category: Choy, R]] | [[Category: Choy, R]] | ||
| + | [[Category: Partridge, J R]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Serine protease]] | ||
| + | [[Category: Small molecule inhibitor]] | ||
Revision as of 04:04, 30 August 2017
Structure of plasma kallikrein protease domain with inhibitor
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