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| | <StructureSection load='5not' size='340' side='right'caption='[[5not]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='5not' size='340' side='right'caption='[[5not]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5not]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NOT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NOT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5not]] 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=5NOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NOT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=938:4-chloranylpyrimidin-5-amine'>938</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=938:4-chloranylpyrimidin-5-amine'>938</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5not FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5not OCA], [http://pdbe.org/5not PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5not RCSB], [http://www.ebi.ac.uk/pdbsum/5not PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5not ProSAT]</span></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=5not FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5not OCA], [https://pdbe.org/5not PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5not RCSB], [https://www.ebi.ac.uk/pdbsum/5not PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5not ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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. | + | [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: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptidylprolyl isomerase]]
| + | [[Category: Georgiou C]] |
| - | [[Category: Georgiou, C]] | + | [[Category: Ioannidis H]] |
| - | [[Category: Ioannidis, H]] | + | [[Category: Julien M]] |
| - | [[Category: Julien, M]] | + | [[Category: Mcnae IW]] |
| - | [[Category: Mcnae, I W]] | + | [[Category: Walkinshaw MD]] |
| - | [[Category: Walkinshaw, M D]] | + | |
| - | [[Category: Beta barrel]]
| + | |
| - | [[Category: Cytosolic]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Ligand complex]]
| + | |
| - | [[Category: Prolyl cis/trans isomerase]]
| + | |
| Structural highlights
Function
PPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Publication Abstract from PubMed
Fragment-based drug discovery is an increasingly popular method to identify novel small-molecule drug candidates. One of the limitations of the approach is the difficulty of accurately characterizing weak binding events. This work reports a combination of X-ray diffraction, surface plasmon resonance experiments and molecular dynamics simulations for the characterization of binders to different isoforms of the cyclophilin (Cyp) protein family. Although several Cyp inhibitors have been reported in the literature, it has proven challenging to achieve high binding selectivity for different isoforms of this protein family. The present studies have led to the identification of several structurally novel fragments that bind to diverse Cyp isoforms in distinct pockets with low millimolar dissociation constants. A detailed comparison of the merits and drawbacks of the experimental and computational techniques is presented, and emerging strategies for designing ligands with enhanced isoform specificity are described.
Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders.,Georgiou C, McNae I, Wear M, Ioannidis H, Michel J, Walkinshaw M J Mol Biol. 2017 Aug 4;429(16):2556-2570. doi: 10.1016/j.jmb.2017.06.016. Epub, 2017 Jun 30. PMID:28673552[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Georgiou C, McNae I, Wear M, Ioannidis H, Michel J, Walkinshaw M. Pushing the Limits of Detection of Weak Binding Using Fragment-Based Drug Discovery: Identification of New Cyclophilin Binders. J Mol Biol. 2017 Aug 4;429(16):2556-2570. doi: 10.1016/j.jmb.2017.06.016. Epub, 2017 Jun 30. PMID:28673552 doi:http://dx.doi.org/10.1016/j.jmb.2017.06.016
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