2k5b
From Proteopedia
Human CDC37-HSP90 docking model based on NMR
Structural highlights
Function[HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.[1] [2] [CDC37_HUMAN] Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.[3] 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 PubMedThe 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. The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy.,Sreeramulu S, Jonker HR, Langer T, Richter C, Lancaster CR, Schwalbe H J Biol Chem. 2009 Feb 6;284(6):3885-96. Epub 2008 Dec 10. PMID:19073599[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Human | Large Structures | Jonker, H R.A | Lancaster, C R | Langer, T | Richter, C | Schwalbe, H | Sreeramulu, S | Alternative splicing | Atp-binding | Cdc37 | Chaperone | Cytoplasm | Heat shock protein | Hsp90 | Nucleotide-binding | P50 | Phosphoprotein | Polymorphism | Protein-protein interaction | Stress response
