View source for 3vha


==Hsp90 alpha N-terminal domain in complex with a macrocyclic inhibitor==
<StructureSection load='3vha' size='340' side='right' caption='[[3vha]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vha]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VHA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VHA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=VHA:22-METHYL-13,18-DIOXA-7-THIA-3,5-DIAZATETRACYCLO[17.3.1.1~2,6~.1~8,12~]PENTACOSA-1(23),2(25),3,5,8(24),9,11,19,21-NONAEN-4-AMINE'>VHA</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3b24|3b24]], [[3b25|3b25]], [[3b26|3b26]], [[3b27|3b27]], [[3b28|3b28]], [[3vhc|3vhc]], [[3vhd|3vhd]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vha OCA], [http://pdbe.org/3vha PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vha RCSB], [http://www.ebi.ac.uk/pdbsum/3vha PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vha ProSAT]</span></td></tr>
</table>
== 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors, CH5164840 showed high binding affinity for N-terminal Hsp90alpha (K(d)=0.52nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC(50)=0.15muM, NCI-N87 IC(50)=0.066muM). CH5164840 displayed high oral bioavailability in mice (F=70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition=83%).

Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.,Suda A, Koyano H, Hayase T, Hada K, Kawasaki K, Komiyama S, Hasegawa K, Fukami TA, Sato S, Miura T, Ono N, Yamazaki T, Saitoh R, Shimma N, Shiratori Y, Tsukuda T Bioorg Med Chem Lett. 2012 Jan 15;22(2):1136-41. Epub 2011 Dec 1. PMID:22192591<ref>PMID:22192591</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3vha" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Proteins|Heat Shock Proteins]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Fukami, T A]]
[[Category: Ono, N]]
[[Category: Chaperone-chaperone inhibitor complex]]