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1fkd

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Revision as of 10:47, 13 September 2017

FK-506 BINDING PROTEIN: THREE-DIMENSIONAL STRUCTURE OF THE COMPLEX WITH THE ANTAGONIST L-685,818

Structural highlights

1fkd is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

L-685,818 differs only slightly in structure from the immunosuppressive drug FK-506, and both compounds bind with comparable affinity to the 12-kDa FK-506-binding protein (FKBP12), the major intracellular receptor for the drug. Despite these similarities, L-685,818 is a potent antagonist of both the immunosuppressive and toxic effects of the drug. Here, we present a structural analysis of this problem. Although FK-506 and L-685,818 differ greatly in pharmacology, we have found that the three-dimensional structures of their complexes with FKBP12 are essentially identical. Approximately half of each ligand is in contact with the receptor protein, and half is exposed to solvent; the exposed region includes the two sites where the compounds differ. These results indicate that the profound differences in the pharmacology of these two compounds are not caused by any difference in their interaction with FKBP12. Rather, these effects arise because relatively minor changes in the exposed part of a bound ligand have a strong effect on how FKBP12-ligand complexes interact with calcineurin, their putative intracellular target. In addition, FK-506 complexes with FKBP12 proteins from several species all inhibit mammalian calcineurin. Analysis of the three-dimensional structure of the complex with respect to residues conserved among these proteins suggests a small number of surface residues near the bound ligands that may play a critical role in interactions between the protein-drug complex and calcineurin.

FK-506-binding protein: three-dimensional structure of the complex with the antagonist L-685,818.,Becker JW, Rotonda J, McKeever BM, Chan HK, Marcy AI, Wiederrecht G, Hermes JD, Springer JP J Biol Chem. 1993 May 25;268(15):11335-9. PMID:7684380^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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, McKeever BM, Chan HK, Marcy AI, Wiederrecht G, Hermes JD, Springer JP. FK-506-binding protein: three-dimensional structure of the complex with the antagonist L-685,818. J Biol Chem. 1993 May 25;268(15):11335-9. PMID:7684380

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fkd"

Categories: Becker, J W | Mckeever, B M | Rotonda, J | Cis-trans isomerase

@@ Line 1: / Line 1: @@
 ==FK-506 BINDING PROTEIN: THREE-DIMENSIONAL STRUCTURE OF THE COMPLEX WITH THE ANTAGONIST L-685,818==
 <StructureSection load='1fkd' size='340' side='right' caption='[[1fkd]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fkd]] 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=1FKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FKD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fkd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FKD FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=818:18-HYDROXYASCOMYCIN'>818</scene></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=1fkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkd OCA], [http://pdbe.org/1fkd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fkd RCSB], [http://www.ebi.ac.uk/pdbsum/1fkd PDBsum]</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=1fkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkd OCA], [http://pdbe.org/1fkd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fkd RCSB], [http://www.ebi.ac.uk/pdbsum/1fkd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fkd ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1fkd ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Becker, J W]]
 [[Category: Mckeever, B M]]
 [[Category: Rotonda, J]]
 [[Category: Cis-trans isomerase]]

1fkd

From Proteopedia

Revision as of 10:47, 13 September 2017

FK-506 BINDING PROTEIN: THREE-DIMENSIONAL STRUCTURE OF THE COMPLEX WITH THE ANTAGONIST L-685,818

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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