PDBsum entry 2k5b

Chaperone

PDB id: 2k5b

Contents

Protein chains

210 a.a. *

129 a.a. *

* Residue conservation analysis

PDB id:

2k5b

Name:

Chaperone

Title:

Human cdc37-hsp90 docking model based on nmr

Structure:

Heat shock protein hsp 90-alpha. Chain: a. Fragment: residues 14-223. Synonym: hsp 86, renal carcinoma antigen ny-ren-38. Engineered: yes. Hsp90 co-chaperone cdc37. Chain: b. Fragment: residues 148-276. Synonym: hsp90 chaperone protein kinase-targeting subunit, p50cdc37.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hsp90aa1, hsp90a, hspc1, hspca. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: cdc37, cdc37a.

NMR struc:

10 models

Authors:

S.Sreeramulu,H.R.A.Jonker,C.R.Lancaster,C.Richter,T.Langer,H.Schwalbe

Key ref:

S.Sreeramulu et al. (2009). The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy. J Biol Chem, 284, 3885-3896. PubMed id: 19073599 DOI: 10.1074/jbc.M806715200

Date:

26-Jun-08 Release date: 09-Dec-08

Protein chain

P07900  (HS90A_HUMAN) -  Heat shock protein HSP 90-alpha from Homo sapiens

Seq: 732 a.a.

Struc: 210 a.a.*

Protein chain

Q16543  (CDC37_HUMAN) -  Hsp90 co-chaperone Cdc37 from Homo sapiens

Seq: 378 a.a.

Struc: 129 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chain A: E.C.3.6.4.10 - non-chaperonin molecular chaperone ATPase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺
• Enzyme class 2: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M806715200

J Biol Chem 284:3885-3896 (2009)

PubMed id: 19073599

The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy.

S.Sreeramulu, H.R.Jonker, T.Langer, C.Richter, C.R.Lancaster, H.Schwalbe.

ABSTRACT

The cell division cycle protein 37 (Cdc37) and the 90-kDa heat shock protein (Hsp90) are molecular chaperones, which are crucial elements in the protein signaling pathway. The largest class of client proteins for Cdc37 and Hsp90 are protein kinases. The catalytic domains of these kinases are stabilized by Cdc37, and their proper folding and functioning is dependent on Hsp90. Here, we present the x-ray crystal structure of the 16-kDa middle domain of human Cdc37 at 1.88 angstroms resolution and the structure of this domain in complex with the 23-kDa N-terminal domain of human Hsp90 based on heteronuclear solution state NMR data and docking. Our results demonstrate that the middle domain of Cdc37 exists as a monomer. NMR and mutagenesis experiments reveal Leu-205 in Cdc37 as a key residue enabling complex formation. These findings can be very useful in the development of small molecule inhibitors against cancer.

Selected figure(s)

Figure 6.
Schematic representation of the interaction interface of NMR calculated Cdc37[M]·Hsp90[N] complex structure. The positively charged, negatively charged, neutral, and hydrophobic amino acids are colored in red, blue, green, and gray, respectively.

Figure 8.
Sequence alignment of human Hsp90[N] and yeast Hsp90[N]. The shaded region is the region that interacts with Cdc37[M] and forms the hydrophobic core of the interface.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 3885-3896) copyright 2009.

Figures were selected by an automated process.