5mim: Difference between revisions
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==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]] | |||
Latest revision as of 21:44, 1 November 2023
Xray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1nXray structure of human furin bound with the 2,5-dideoxystreptamine derived small molecule inhibitor 1n
Structural highlights
FunctionFURIN_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.[1] Publication Abstract from PubMedProprotein 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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