View source for 6hza


==X-ray structure of furin in complex with the cyclic peptide c[glutaryl-Arg-Arg-Lys]-Arg-4-Amba==
<StructureSection load='6hza' size='340' side='right'caption='[[6hza]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6hza]] 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=6HZA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HZA 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]] 1.9&#8491;</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PTD:PENTANEDIAL'>PTD</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=6hza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hza OCA], [https://pdbe.org/6hza PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hza RCSB], [https://www.ebi.ac.uk/pdbsum/6hza PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hza 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> 
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== Publication Abstract from PubMed ==
The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.

Design, Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin.,Lam van TV, Ivanova T, Hardes K, Heindl MR, Morty RE, Bottcher-Friebertshauser E, Lindberg I, Than ME, Dahms SO, Steinmetzer T ChemMedChem. 2019 Jan 25. doi: 10.1002/cmdc.201800807. PMID:30680958<ref>PMID:30680958</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6hza" style="background-color:#fffaf0;"></div>

==See Also==
*[[Furin|Furin]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Dahms SO]]