5mim
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Xray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1n== | |
| + | <StructureSection load='5mim' size='340' side='right'caption='[[5mim]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5mim]] is a 1 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=5MIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MIM FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1N:1-[(1~{R},2~{R},4~{S},5~{S})-2,4-BIS(4-CARBAMIMIDAMIDOPHENOXY)-5-[(4-CARBAMIMIDAMIDOPHENYL)AMINO]CYCLOHEXYL]GUANIDINE'>1N</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5mim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mim OCA], [https://pdbe.org/5mim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mim RCSB], [https://www.ebi.ac.uk/pdbsum/5mim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mim ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FURIN_HUMAN FURIN_HUMAN] Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.<ref>PMID:7690548</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Proprotein convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of several pathologies including cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Here, we present the first experimental complex of furin with a non-substrate-like small molecule inhibitor, and the X-ray structure of the enzyme complexed to the small molecule inhibitor 1 at 1.9 A resolution. Two molecules of inhibitor 1 were found to interact with furin. One is anchored at the S4 pocket of the enzyme and interferes directly with the conformation and function of the catalytic triade; the other molecule shows weaker binding and interacts with a distant, less conserved region of furin. The observed binding modes represent a new inhibition strategy of furin and imply the possibility to attain specificity among the PCs providing an innovative starting point of structure guided inhibitor development for furin. | ||
| - | + | Structural Studies Revealed Active Site Distortions of Human Furin by a Small Molecule Inhibitor.,Dahms SO, Jiao GS, Than ME ACS Chem Biol. 2017 Apr 17. doi: 10.1021/acschembio.6b01110. PMID:28402100<ref>PMID:28402100</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5mim" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Furin|Furin]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dahms SO]] | ||
| + | [[Category: Guan-Sheng J]] | ||
| + | [[Category: Than ME]] | ||
Current revision
Xray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1n
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