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PDBsum entry 1kt1

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Isomerase PDB id
1kt1
Jmol
Contents
Protein chain
374 a.a. *
Ligands
SO4 ×2
Waters ×31
* Residue conservation analysis

References listed in PDB file
Key reference
Title Structure of the large fk506-Binding protein fkbp51, An hsp90-Binding protein and a component of steroid receptor complexes.
Authors C.R.Sinars, J.Cheung-Flynn, R.A.Rimerman, J.G.Scammell, D.F.Smith, J.Clardy.
Ref. Proc Natl Acad Sci U S A, 2003, 100, 868-873. [DOI no: 10.1073/pnas.0231020100]
PubMed id 12538866
Abstract
The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 A, and squirrel monkey FKBP51, to 2.8 A, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex.
Figure 1.
Fig. 1. Crystal structure of FKBP51. (A) The overall structure is as follows: light green is the FK1 domain, dark green is the FK2 domain, red is the TPR domain, and yellow regions are the linkers between domains. (B) In each case, coordinates of a similar domain (FKBP12, FKBP12, and the Hop TPR 2a domain) bound to a ligand [rapamycin (39), rapamycin, and Hsp90 fragment MEEVD (37), respectively] were superposed on FKBP51s domains (FK1, FK2, and TPR). The resulting ligand coordinates are shown in yellow space-filling atoms. (C) Extensive hydrogen bonding of the linker region between FK1 and FK2. The yellow bonds are the linking regions, dark-green bonds are FK2, and light-green bonds are FK1. Figs. 1-5 were rendered with MOLSCRIPT (34) and RASTER3D (35).
Figure 2.
Fig. 2. Binding pocket of FK1. FKBP12 (yellow with black labels) coordinates were superposed with FK1 of FKBP51 (green with green labels). Only one amino acid differs, at H87 FKBP51, which instead has a serine. The remaining side chains superpose well.
PROCHECK
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