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| | <StructureSection load='1qpl' size='340' side='right'caption='[[1qpl]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='1qpl' size='340' side='right'caption='[[1qpl]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1qpl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QPL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1qpl]] is a 2 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=1QPL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QPL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=587:C32-O-(1-METHYL-INDOL-5-YL)+18-HYDROXY-ASCOMYCIN'>587</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]] 2.9Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=587:C32-O-(1-METHYL-INDOL-5-YL)+18-HYDROXY-ASCOMYCIN'>587</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=1qpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qpl OCA], [https://pdbe.org/1qpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qpl RCSB], [https://www.ebi.ac.uk/pdbsum/1qpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qpl 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=1qpl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qpl OCA], [https://pdbe.org/1qpl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qpl RCSB], [https://www.ebi.ac.uk/pdbsum/1qpl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qpl ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN]] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref>
| + | [https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Becker, J W]] | + | [[Category: Becker JW]] |
| - | [[Category: Rotonda, J]] | + | [[Category: Rotonda J]] |
| - | [[Category: Cis-trans isomerase]]
| + | |
| - | [[Category: Immunophilin-drug complex]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Peptidyl-prolyl isomerase]]
| + | |
| Structural highlights
Function
FKB1A_HUMAN Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.[1] [2]
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
32-Indole ether derivatives of tacrolimus and ascomycin retain the potent immunosuppressive activity of their parent compounds but display reduced toxicity. In addition, their complexes with the 12-kDa FK506-binding protein (FKBP) form more stable complexes with the protein phosphatase calcineurin, the molecular target of these drugs. We have solved the three-dimensional structures of the FKBP complexes with two 32-indolyl derivatives of ascomycin. The structures of the protein and the macrolide are remarkably similar to those seen in the complexes with tacrolimus and ascomycin. The indole groups project away from the body of the complex, and multiple conformations are observed for the linkage to these groups as well as for a nearby peptide suggesting apparent flexibility in these parts of the structure. Comparison of these structures with that of the ternary complex of calcineurin, FKBP, and tacrolimus suggests that the indole groups interact with a binding site comprising elements of both the calcineurin alpha- and beta-chains and that this interaction is responsible for the increased stability of these complexes.
32-Indolyl ether derivatives of ascomycin: three-dimensional structures of complexes with FK506-binding protein.,Becker JW, Rotonda J, Cryan JG, Martin M, Parsons WH, Sinclair PJ, Wiederrecht G, Wong F J Med Chem. 1999 Jul 29;42(15):2798-804. PMID:10425089[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen YG, Liu F, Massague J. Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J. 1997 Jul 1;16(13):3866-76. PMID:9233797 doi:10.1093/emboj/16.13.3866
- ↑ Yamaguchi T, Kurisaki A, Yamakawa N, Minakuchi K, Sugino H. FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. J Mol Endocrinol. 2006 Jun;36(3):569-79. PMID:16720724 doi:10.1677/jme.1.01966
- ↑ Becker JW, Rotonda J, Cryan JG, Martin M, Parsons WH, Sinclair PJ, Wiederrecht G, Wong F. 32-Indolyl ether derivatives of ascomycin: three-dimensional structures of complexes with FK506-binding protein. J Med Chem. 1999 Jul 29;42(15):2798-804. PMID:10425089 doi:http://dx.doi.org/10.1021/jm9806042
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