View source for 5n7q


==CRYSTAL STRUCTURE OF MATURE CATHEPSIN D FROM THE TICK IXODES RICINUS (IRCD1) IN COMPLEX WITH THE INHIBITOR PEPSTATIN A==
<StructureSection load='5n7q' size='340' side='right'caption='[[5n7q]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5n7q]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinomycetia Actinomycetia] and [https://en.wikipedia.org/wiki/Ixodes_ricinus Ixodes ricinus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N7Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N7Q 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]] 1.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IVA:ISOVALERIC+ACID'>IVA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=STA:STATINE'>STA</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=5n7q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n7q OCA], [https://pdbe.org/5n7q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n7q RCSB], [https://www.ebi.ac.uk/pdbsum/5n7q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n7q ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/V5HCK7_IXORI V5HCK7_IXORI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pepsin-family aspartic peptidases are biosynthesized as inactive zymogens in which the propeptide blocks the active site until its proteolytic removal upon enzyme activation. Here, we describe a novel dual regulatory function for the propeptide using a set of crystal structures of the parasite cathepsin D IrCD1. In the IrCD1 zymogen, intramolecular autoinhibition by the intact propeptide is mediated by an evolutionarily conserved exosite on the enzyme core. After activation, the mature enzyme employs the same exosite to rebind a small fragment derived from the cleaved propeptide. This fragment functions as an effective natural inhibitor of mature IrCD1 that operates in a pH-dependent manner through a unique allosteric inhibition mechanism. The study uncovers the propeptide-binding exosite as a target for the regulation of pepsin-family aspartic peptidases and defines the structural requirements for exosite inhibition.

Novel Structural Mechanism of Allosteric Regulation of Aspartic Peptidases via an Evolutionarily Conserved Exosite.,Hanova I, Brynda J, Houstecka R, Alam N, Sojka D, Kopacek P, Maresova L, Vondrasek J, Horn M, Schueler-Furman O, Mares M Cell Chem Biol. 2018 Jan 26. pii: S2451-9456(18)30001-1. doi:, 10.1016/j.chembiol.2018.01.001. PMID:29396291<ref>PMID:29396291</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5n7q" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Actinomycetia]]
[[Category: Ixodes ricinus]]
[[Category: Large Structures]]
[[Category: Brynda J]]
[[Category: Hanova I]]
[[Category: Hobizalova R]]
[[Category: Mares M]]