6yd4: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==X-ray structure of furin in complex with the canavanine-based inhibitor 4-guanidinomethyl-phenylacetyl-Canavanine-Tle-Canavanine-Amba== | ==X-ray structure of furin in complex with the canavanine-based inhibitor 4-guanidinomethyl-phenylacetyl-Canavanine-Tle-Canavanine-Amba== | ||
<StructureSection load='6yd4' size='340' side='right'caption='[[6yd4]]' scene=''> | <StructureSection load='6yd4' size='340' side='right'caption='[[6yd4]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YD4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6yd4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YD4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YD4 FirstGlance]. <br> | ||
</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=6yd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yd4 OCA], [https://pdbe.org/6yd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yd4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yd4 ProSAT]</span></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]] 1.7Å</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=3U0:2-[4-(carbamimidamidomethyl)phenyl]ethanoic+acid'>3U0</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GGB:L-CANAVANINE'>GGB</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TBG:3-METHYL-L-VALINE'>TBG</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=6yd4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yd4 OCA], [https://pdbe.org/6yd4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yd4 RCSB], [https://www.ebi.ac.uk/pdbsum/6yd4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yd4 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
Furin activates numerous viral glycoproteins, and its inhibition prevents virus replication and spread. Through the replacement of arginine by the less basic canavanine, new inhibitors targeting furin in the trans-Golgi network were developed. These inhibitors exert potent antiviral activity in cell culture with much lower toxicity than arginine-derived analogues, most likely due to their reduced protonation in the blood circulation. Thus, despite its important physiological functions, furin might be a suitable antiviral drug target. | |||
The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin.,Lam van TV, Heindl MR, Schlutt C, Bottcher-Friebertshauser E, Bartenschlager R, Klebe G, Brandstetter H, Dahms SO, Steinmetzer T ACS Med Chem Lett. 2021 Feb 9;12(3):426-432. doi: 10.1021/acsmedchemlett.0c00651., eCollection 2021 Mar 11. PMID:33732412<ref>PMID:33732412</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6yd4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Furin|Furin]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Synthetic construct]] | |||
[[Category: Dahms SO]] | [[Category: Dahms SO]] | ||