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| | ==X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba== | | ==X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba== |
| - | <StructureSection load='4omc' size='340' side='right' caption='[[4omc]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4omc' size='340' side='right'caption='[[4omc]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4omc]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OMC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OMC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4omc]] is a 12 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=4OMC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OMC 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=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=00S:4-(AMINOMETHYL)BENZENECARBOXIMIDAMIDE'>00S</scene>, <scene name='pdbligand=2UC:1-[3-(2-OXOETHYL)BENZYL]GUANIDINE'>2UC</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=00S:4-(AMINOMETHYL)BENZENECARBOXIMIDAMIDE'>00S</scene>, <scene name='pdbligand=2UC:1-[3-(2-OXOETHYL)BENZYL]GUANIDINE'>2UC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PRD_001220:meta-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)benzamidine'>PRD_001220</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4omd|4omd]], [[1p8j|1p8j]]</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=4omc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4omc OCA], [https://pdbe.org/4omc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4omc RCSB], [https://www.ebi.ac.uk/pdbsum/4omc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4omc ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FUR, FURIN, PACE, PCSK3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Furin Furin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.75 3.4.21.75] </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=4omc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4omc OCA], [http://pdbe.org/4omc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4omc RCSB], [http://www.ebi.ac.uk/pdbsum/4omc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4omc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4omc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4omc" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Furin|Furin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Furin]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Dahms, S O]] | + | [[Category: Dahms SO]] |
| - | [[Category: Than, M E]] | + | [[Category: Than ME]] |
| - | [[Category: Competitive inhibitor]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Pro-protein convertase]]
| + | |
| - | [[Category: Protease-inhibitor complex]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| Structural highlights
4omc is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.3Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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.[1]
Publication Abstract from PubMed
Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus. Development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. Here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with noncovalent inhibitors. We show the inhibitor exchange by soaking, allowing the investigation of additional inhibitors and substrate analogues. Thus, our work provides a basis for the rational design of furin inhibitors.
X-ray Structures of Human Furin in Complex with Competitive Inhibitors.,Dahms SO, Hardes K, Becker GL, Steinmetzer T, Brandstetter H, Than ME ACS Chem Biol. 2014 Apr 1. PMID:24666235[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takahashi S, Kasai K, Hatsuzawa K, Kitamura N, Misumi Y, Ikehara Y, Murakami K, Nakayama K. A mutation of furin causes the lack of precursor-processing activity in human colon carcinoma LoVo cells. Biochem Biophys Res Commun. 1993 Sep 15;195(2):1019-26. PMID:7690548 doi:http://dx.doi.org/10.1006/bbrc.1993.2146
- ↑ Dahms SO, Hardes K, Becker GL, Steinmetzer T, Brandstetter H, Than ME. X-ray Structures of Human Furin in Complex with Competitive Inhibitors. ACS Chem Biol. 2014 Apr 1. PMID:24666235 doi:http://dx.doi.org/10.1021/cb500087x
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