5lud: Difference between revisions
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<StructureSection load='5lud' size='340' side='right'caption='[[5lud]], [[Resolution|resolution]] 1.25Å' scene=''> | <StructureSection load='5lud' size='340' side='right'caption='[[5lud]], [[Resolution|resolution]] 1.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5lud]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5lud]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LUD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LUD FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.25Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=76X:PYRIDINE-2,3-DIAMINE'>76X</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=5lud FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lud OCA], [https://pdbe.org/5lud PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lud RCSB], [https://www.ebi.ac.uk/pdbsum/5lud PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lud ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Blackburn EA]] | |||
[[Category: Blackburn | [[Category: McNae IW]] | ||
[[Category: McNae | [[Category: Nowicki MW]] | ||
[[Category: Nowicki | [[Category: Walkinshaw MD]] | ||
[[Category: Walkinshaw | [[Category: Wear MA]] | ||
[[Category: Wear | |||
Latest revision as of 21:49, 18 October 2023
Structure of Cyclophilin A in complex with 2,3-DiaminopyridineStructure of Cyclophilin A in complex with 2,3-Diaminopyridine
Structural highlights
FunctionPPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Publication Abstract from PubMedWe have established a refined methodology for generating surface plasmon resonance sensor surfaces of recombinant his-tagged human cyclophilin-A. Our orientation-specific stabilisation approach captures his-tagged protein under 'physiological conditions' (150 mm NaCl, pH 7.5) and covalently stabilises it on Ni2+-nitrilotriacetic acid surfaces, very briefly activated for primary amine-coupling reactions, producing very stable and active surfaces (>/= 95% specific activity) of cyclophilin-A. Variation in protein concentration with the same contact time allows straightforward generation of variable density surfaces, with essentially no loss of activity, making the protocol easily adaptable for studying numerous interactions; from very small fragments, ~ 100 Da, to large protein ligands. This new method results in an increased stability and activity of the immobilised protein and allowed us to expand the thermo-kinetic analysis space, and to determine accurate and robust thermodynamic parameters for the cyclophilin-A-cyclosporin-A interaction. Furthermore, the increased sensitivity of the surface allowed identification of a new nonpeptide inhibitor of cyclophilin-A, from a screen of a fragment library. This fragment, 2,3-diaminopyridine, bound specifically with a mean affinity of 248 +/- 60 mum. The X-ray structure of this 109-Da fragment bound in the active site of cyclophilin-A was solved to a resolution of 1.25 A (PDB: 5LUD), providing new insight into the molecular details for a potential new series of nonpeptide cyclophilin-A inhibitors. Thermo-kinetic analysis space expansion for cyclophilin-ligand interactions - identification of a new nonpeptide inhibitor using Biacore T200.,Wear MA, Nowicki MW, Blackburn EA, McNae IW, Walkinshaw MD FEBS Open Bio. 2017 Feb 23;7(4):533-549. doi: 10.1002/2211-5463.12201., eCollection 2017 Apr. PMID:28396838[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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