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| | ==Crystal structure of cyclophilin ABH-like domain of human peptidylprolyl isomerase E isoform 1== | | ==Crystal structure of cyclophilin ABH-like domain of human peptidylprolyl isomerase E isoform 1== |
| - | <StructureSection load='2r99' size='340' side='right' caption='[[2r99]], [[Resolution|resolution]] 1.61Å' scene=''> | + | <StructureSection load='2r99' size='340' side='right'caption='[[2r99]], [[Resolution|resolution]] 1.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2r99]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1zcx 1zcx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R99 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R99 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2r99]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1zcx 1zcx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R99 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIE, CYP33 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.61Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=2r99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r99 OCA], [https://pdbe.org/2r99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r99 RCSB], [https://www.ebi.ac.uk/pdbsum/2r99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r99 ProSAT]</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=2r99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r99 OCA], [http://pdbe.org/2r99 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r99 RCSB], [http://www.ebi.ac.uk/pdbsum/2r99 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2r99 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPIE_HUMAN PPIE_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Combines RNA-binding and PPIase activities. May be involved in muscle- and brain-specific processes. May be involved in pre-mRNA splicing. | + | [https://www.uniprot.org/uniprot/PPIE_HUMAN PPIE_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Combines RNA-binding and PPIase activities. May be involved in muscle- and brain-specific processes. May be involved in pre-mRNA splicing. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2r99" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2r99" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Davis, T]] | + | [[Category: Davis T]] |
| - | [[Category: Dhe-Paganon, S]] | + | [[Category: Dhe-Paganon S]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Mackenzie, F]] | + | [[Category: Mackenzie F]] |
| - | [[Category: Newman, E M]] | + | [[Category: Newman EM]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Walker JR]] |
| - | [[Category: Walker, J R]] | + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Cis-trans isomerization]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Mrna processing]]
| + | |
| - | [[Category: Mrna splicing]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Rna-binding]]
| + | |
| - | [[Category: Rotamase]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Spliceosome]]
| + | |
| Structural highlights
Function
PPIE_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Combines RNA-binding and PPIase activities. May be involved in muscle- and brain-specific processes. May be involved in pre-mRNA splicing.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Peptidyl-prolyl isomerases catalyze the conversion between cis and trans isomers of proline. The cyclophilin family of peptidyl-prolyl isomerases is well known for being the target of the immunosuppressive drug cyclosporin, used to combat organ transplant rejection. There is great interest in both the substrate specificity of these enzymes and the design of isoform-selective ligands for them. However, the dearth of available data for individual family members inhibits attempts to design drug specificity; additionally, in order to define physiological functions for the cyclophilins, definitive isoform characterization is required. In the current study, enzymatic activity was assayed for 15 of the 17 human cyclophilin isomerase domains, and binding to the cyclosporin scaffold was tested. In order to rationalize the observed isoform diversity, the high-resolution crystallographic structures of seven cyclophilin domains were determined. These models, combined with seven previously solved cyclophilin isoforms, provide the basis for a family-wide structure:function analysis. Detailed structural analysis of the human cyclophilin isomerase explains why cyclophilin activity against short peptides is correlated with an ability to ligate cyclosporin and why certain isoforms are not competent for either activity. In addition, we find that regions of the isomerase domain outside the proline-binding surface impart isoform specificity for both in vivo substrates and drug design. We hypothesize that there is a well-defined molecular surface corresponding to the substrate-binding S2 position that is a site of diversity in the cyclophilin family. Computational simulations of substrate binding in this region support our observations. Our data indicate that unique isoform determinants exist that may be exploited for development of selective ligands and suggest that the currently available small-molecule and peptide-based ligands for this class of enzyme are insufficient for isoform specificity.
Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases.,Davis TL, Walker JR, Campagna-Slater V, Finerty PJ, Paramanathan R, Bernstein G, MacKenzie F, Tempel W, Ouyang H, Lee WH, Eisenmesser EZ, Dhe-Paganon S PLoS Biol. 2010 Jul 27;8(7):e1000439. doi: 10.1371/journal.pbio.1000439. PMID:20676357[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Davis TL, Walker JR, Campagna-Slater V, Finerty PJ, Paramanathan R, Bernstein G, MacKenzie F, Tempel W, Ouyang H, Lee WH, Eisenmesser EZ, Dhe-Paganon S. Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases. PLoS Biol. 2010 Jul 27;8(7):e1000439. doi: 10.1371/journal.pbio.1000439. PMID:20676357 doi:http://dx.doi.org/10.1371/journal.pbio.1000439
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