View source for Hsp90 co-chaperone Cdc37

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{{#invoke:InfoboxforTarget|run|CDC37|[https://www.uniprot.org/uniprot/Q16543 Q16543]|Homo sapiens|Cys57, Cys54, Cys64|[http://pfam.xfam.org/family/PF03234 CDC37 family]|[[:Category:Hsp90 co-chaperone Cdc37|Ligand list]]|Chaperone}}
==Summary==

===Protein Function ===
Hsp90 co-chaperone Cdc37 is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF1, MOK, as well as eIF-2 alpha kinases, and is upregulated in various cancers. It is thought to play a critical role in directing Hsp90 to its target kinases. The protein–protein complex forms with a KD value of 1.2 mm and is considered to mediate carcinogenesis by stabilizing a variety of different oncogenic kinases in malignant cells.<br/>
CDC37 consists of three structural domains. The N-terminal domain binds to protein kinases. The central domain is the Hsp90chaperone (heat shock protein 90) binding domain. The function of the C-terminal domain is unclear. (From Uniprot, Wikipedia, PMID: 19585625)<br/>

===Cys Function & Property===
From the mutation, homology modeling and other assay, Cys57, Cys54, Cys64 are confirmed to located in/near the celastrol binding pocket. <br/>
[[File:579-function.png|center|600px]]
<div align="center">Possible mechanisms of inactivation of Cdc37 by celastrol</div>
[[File:579-function2.png|center|600px]]
<div align="center">The predicted model of Cdc37_NM complexed with celastrol</div>

* Hydrophobic property:
:[[File:579-hydro.png||600px]]
* SASA:
:Unknown<br/>

==Protein Sequence==
<font face="Courier">
MVDYSVWDHI EVSDDEDETH PNIDTASLFR WRHQARVERM EQFQKEKEEL <br/>
DRG<span style="background:#ffff00">'''C'''</span>RE<span style="background:#ffff00">'''C'''</span>KRK VAE<span style="background:#ffff00">'''C'''</span>QRKLKE LEVAEGGKAE LERLQAEAQQ LRKEERSWEQ <br/>
KLEEMRKKEK SMPWNVDTLS KDGFSKSMVN TKPEKTEEDS EEVREQKHKT <br/>
FVEKYEKQIK HFGMLRRWDD SQKYLSDNVH LVCEETANYL VIWCIDLEVE <br/>
EKCALMEQVA HQTIVMQFIL ELAKSLKVDP RACFRQFFTK IKTADRQYME <br/>
GFNDELEAFK ERVRGRAKLR IEKAMKEYEE EERKKRLGPG GLDPVEVYES <br/>
LPEELQKCFD VKDVQMLQDA ISKMDPTDAK YHMQRCIDSG LWVPNSKASE <br/>
AKEGEEAGPG DPLLEAVPKT GDEKDVSV                         <br/> 
</font>

==Structural Information==
*Known structure with covalent ligand: <br/>
:Unknown <br/>

*Protein structure:
:Unknown <br/>

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko04151 PI3K-Akt signaling pathway] <br/>

==Experimental Evidence==
:Nuclear Magnetic Resonance, Mass Spectrometry    

==Reference==
# Sreeramulu S, Gande S L, Göbel M, et al. '''Molecular mechanism of inhibition of the human protein complex Hsp90–Cdc37, a kinome chaperone–cochaperone, by triterpene celastrol[J].''' Angewandte Chemie International Edition, 2009, 48(32): 5853-5855. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19585625 19585625]<br/>  
# Duan Y, Jin H, Yu H, et al. '''Computational investigation of interactions between Cdc37 and celastrol[J].''' Molecular Simulation, 2013, 39(4): 270-278. DOI:10.1080/08927022.2012.718439.

[[Category:Targets]]
[[Category:Homo sapiens]]
[[Category:Chaperone]]
[[Category:CDC37 family]]
[[Category:PI3K-Akt signaling pathway]]