View source for 6gjr


==Cyclophilin A complexed with tri-vector ligand 9.==
<StructureSection load='6gjr' size='340' side='right' caption='[[6gjr]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gjr]] is a 1 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=6GJR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GJR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F0W:ethyl+2-[[(4-aminophenyl)methyl-[(2-methyl-1,2,3,4-tetrazol-5-yl)methyl]carbamoyl]amino]ethanoate'>F0W</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIA, CYPA ([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/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=6gjr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gjr OCA], [http://pdbe.org/6gjr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gjr RCSB], [http://www.ebi.ac.uk/pdbsum/6gjr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gjr ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclophilins (Cyps) are a major family of drug targets that are challenging to prosecute with small molecules because the shallow nature and high degree of conservation of the active site across human isoforms offers limited opportunities for potent and selective inhibition. Herein a computational approach based on molecular dynamics simulations and free energy calculations was combined with biophysical assays and X-ray crystallography to explore a flip in the binding mode of a reported urea-based Cyp inhibitor. This approach enabled access to a distal pocket that is poorly conserved among key Cyp isoforms, and led to the discovery of a new family of sub-micromolar cell-active inhibitors that offer unprecedented opportunities for the development of next-generation drug therapies based on Cyp inhibition. The computational approach is applicable to a broad range of organic functional groups and could prove widely enabling in molecular design.

A computationally designed binding mode flip leads to a novel class of potent tri-vector cyclophilin inhibitors.,De Simone A, Georgiou C, Ioannidis H, Gupta AA, Juarez-Jimenez J, Doughty-Shenton D, Blackburn EA, Wear MA, Richards JP, Barlow PN, Carragher N, Walkinshaw MD, Hulme AN, Michel J Chem Sci. 2018 Oct 23;10(2):542-547. doi: 10.1039/c8sc03831g. eCollection 2019, Jan 14. PMID:30746096<ref>PMID:30746096</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6gjr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Georgiou, C]]
[[Category: Michel, J]]
[[Category: Simone, A De]]
[[Category: Walkinshaw, M D]]
[[Category: Complex]]
[[Category: Cyclophilin]]
[[Category: Cypa]]
[[Category: Inhibitor]]
[[Category: Isomerase]]
[[Category: Ppiase]]