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PDBsum entry 4lax
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PDB id:
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Isomerase
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Title:
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Crystal structure analysis of fkbp52, complex with fk506
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Structure:
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Peptidyl-prolyl cis-trans isomerase fkbp4. Chain: a. Fragment: unp residues 16-260. Synonym: ppiase fkbp4, 52 kda fk506-binding protein, 52 kda fkbp, fkbp-52, 59 kda immunophilin, p59, fk506-binding protein 4, fkbp-4, fkbp59, hsp-binding immunophilin, hbi, immunophilin fkbp52, rotamase. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: fkbp4, fkbp52. Expressed in: escherichia coli. Expression_system_taxid: 469008.
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Resolution:
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2.01Å
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R-factor:
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0.185
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R-free:
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0.219
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Authors:
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A.Bracher,C.Kozany,A.Haehle,P.Wild,M.Zacharias,F.Hausch
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Key ref:
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A.Bracher
et al.
(2013).
Crystal structures of the free and ligand-bound FK1-FK2 domain segment of FKBP52 reveal a flexible inter-domain hinge.
J Mol Biol,
425,
4134-4144.
PubMed id:
DOI:
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Date:
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20-Jun-13
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Release date:
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21-Aug-13
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PROCHECK
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Headers
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References
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Q02790
(FKBP4_HUMAN) -
Peptidyl-prolyl cis-trans isomerase FKBP4 from Homo sapiens
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Seq:
Struc:
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459 a.a.
237 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.5.2.1.8
- peptidylprolyl isomerase.
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Reaction:
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[protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
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Peptidylproline (omega=180)
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=
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peptidylproline (omega=0)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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J Mol Biol
425:4134-4144
(2013)
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PubMed id:
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Crystal structures of the free and ligand-bound FK1-FK2 domain segment of FKBP52 reveal a flexible inter-domain hinge.
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A.Bracher,
C.Kozany,
A.Hähle,
P.Wild,
M.Zacharias,
F.Hausch.
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ABSTRACT
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The human Hsp90 co-chaperone FKBP52 belongs to the family of FK506-binding
proteins, which act as peptidyl-prolyl isomerases. FKBP52 specifically enhances
the signaling of steroid hormone receptors, modulates ion channels and regulates
neuronal outgrowth dynamics. In turn, small-molecule ligands of FKBP52 have been
suggested as potential neurotrophic or anti-prostate cancer agents. The
usefulness of available ligands is however limited by a lack of selectivity. The
immunophilin FKBP52 is composed of three domains, an FK506-binding domain with
peptidyl-prolyl isomerase activity, an FKBP-like domain of unknown function and
a TPR-clamp domain, which recognizes the C-terminal peptide of Hsp90 with high
affinity. The herein reported crystal structures of FKBP52 reveal that the short
linker connecting the FK506-binding domain and the FKBP-like domain acts as a
flexible hinge. This enhanced flexibility and its modulation by phosphorylation
might explain some of the functional antagonism between the closely related
homologs FKBP51 and FKBP52. We further present two co-crystal structures of
FKBP52 in complex with the prototypic ligand FK506 and a synthetic analog
thereof. These structures revealed the molecular interactions in great detail,
which enabled in-depth comparison with the corresponding complexes of the other
cytosolic FKBPs, FKBP51 and FKBP12. The observed subtle differences provide
crucial insights for the rational design of ligands with improved selectivity
for FKBP52.
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