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| | ==Human CDC37-HSP90 docking model based on NMR== | | ==Human CDC37-HSP90 docking model based on NMR== |
| - | <StructureSection load='2k5b' size='340' side='right' caption='[[2k5b]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2k5b' size='340' side='right'caption='[[2k5b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k5b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K5B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K5B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k5b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K5B FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1yes|1yes]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CDC37, CDC37A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k5b OCA], [https://pdbe.org/2k5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k5b RCSB], [https://www.ebi.ac.uk/pdbsum/2k5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k5b ProSAT]</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=2k5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k5b OCA], [http://pdbe.org/2k5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2k5b RCSB], [http://www.ebi.ac.uk/pdbsum/2k5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2k5b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HS90A_HUMAN 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.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> [[http://www.uniprot.org/uniprot/CDC37_HUMAN 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.<ref>PMID:8666233</ref> | + | [https://www.uniprot.org/uniprot/HS90A_HUMAN 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.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Heat Shock Proteins|Heat Shock Proteins]] | + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Jonker, H R.A]] | + | [[Category: Large Structures]] |
| - | [[Category: Lancaster, C R]] | + | [[Category: Jonker HRA]] |
| - | [[Category: Langer, T]] | + | [[Category: Lancaster CR]] |
| - | [[Category: Richter, C]] | + | [[Category: Langer T]] |
| - | [[Category: Schwalbe, H]] | + | [[Category: Richter C]] |
| - | [[Category: Sreeramulu, S]] | + | [[Category: Schwalbe H]] |
| - | [[Category: Alternative splicing]]
| + | [[Category: Sreeramulu S]] |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Cdc37]]
| + | |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Heat shock protein]]
| + | |
| - | [[Category: Hsp90]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: P50]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Protein-protein interaction]]
| + | |
| - | [[Category: Stress response]]
| + | |
| 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]
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
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
- ↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
- ↑ Sreeramulu S, Jonker HR, Langer T, Richter C, Lancaster CR, Schwalbe H. The human Cdc37.Hsp90 complex studied by heteronuclear NMR spectroscopy. J Biol Chem. 2009 Feb 6;284(6):3885-96. Epub 2008 Dec 10. PMID:19073599 doi:10.1074/jbc.M806715200
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