View source for 5jxh


==Structure the proprotein convertase furin in complex with meta-guanidinomethyl-Phac-RVR-Amba at 2.0 Angstrom resolution.==
<StructureSection load='5jxh' size='340' side='right'caption='[[5jxh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jxh]] 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=5JXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JXH 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]] 2&#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=2UC:1-[3-(2-OXOETHYL)BENZYL]GUANIDINE'>2UC</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=5jxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jxh OCA], [https://pdbe.org/5jxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jxh RCSB], [https://www.ebi.ac.uk/pdbsum/5jxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jxh 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 ==
Proprotein convertases (PCs) are highly specific proteases required for the proteolytic modification of many secreted proteins. An unbalanced activity of these enzymes is connected to pathologies like cancer, atherosclerosis, hypercholesterolaemia, and infectious diseases. Novel protein crystallographic structures of the prototypical PC family member furin in different functional states were determined to 1.8-2.0 A. These, together with biochemical data and modeling by molecular dynamics calculations, suggest essential elements underlying its unusually high substrate specificity. Furin shows a complex activation mechanism and exists in at least four defined states: (i) the "off state," incompatible with substrate binding as seen in the unliganded enzyme; (ii) the active "on state" seen in inhibitor-bound furin; and the respective (iii) calcium-free and (iv) calcium-bound forms. The transition from the off to the on state is triggered by ligand binding at subsites S1 to S4 and appears to underlie the preferential recognition of the four-residue sequence motif of furin. The molecular dynamics simulations of the four structural states reflect the experimental observations in general and provide approximations of the respective stabilities. Ligation by calcium at the PC-specific binding site II influences the active-site geometry and determines the rotamer state of the oxyanion hole-forming Asn295, and thus adds a second level of the activity modulation of furin. The described crystal forms and the observations of different defined functional states may foster the development of new tools and strategies for pharmacological intervention targeting furin.

Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism.,Dahms SO, Arciniega M, Steinmetzer T, Huber R, Than ME Proc Natl Acad Sci U S A. 2016 Sep 19. pii: 201613630. PMID:27647913<ref>PMID:27647913</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 5jxh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Furin|Furin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Arciniega M]]
[[Category: Dahms SO]]
[[Category: Huber R]]
[[Category: Steinmetzer T]]
[[Category: Than ME]]