View source for 1uy9

[[Image:1uy9.gif|left|200px]]<br />
<applet load="1uy9" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1uy9, resolution 2.00&Aring;" />
'''HUMAN HSP90-ALPHA WITH 8-BENZO[1,3]DIOXOL-,5-YLMETHYL-9-BUTYL-9H-PURIN-6-YLAMINE'''<br />

==Overview==
Inhibition of the ATPase activity of the chaperone protein HSP90 is a, potential strategy for treatment of cancers. We have determined structures, of the HSP90alpha N-terminal domain complexed with the purine-based, inhibitor, PU3, and analogs with enhanced potency both in enzyme and, cell-based assays. The compounds induce upregulation of HSP70 and, downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent, on HSP90 inhibition. We have also determined the first structure of the, N-terminal domain of HSP90beta, complexed with PU3. The structures allow a, detailed rationale to be developed for the observed affinity of the PU3, class of compounds for HSP90 and also provide a structural framework for, ... [[http://ispc.weizmann.ac.il/pmbin/getpm?15217611 (full description)]]

==About this Structure==
1UY9 is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with PU6 as [[http://en.wikipedia.org/wiki/ligand ligand]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1UY9 OCA]]. 

==Reference==
Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms., Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE, Chem Biol. 2004 Jun;11(6):775-85. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15217611 15217611]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Aherne, W.]]
[[Category: Barril, X.]]
[[Category: Beswick, M.]]
[[Category: Boxall, K.]]
[[Category: Collier, A.]]
[[Category: Davies, N.]]
[[Category: Drysdale, M.]]
[[Category: Dymock, B.]]
[[Category: Fink, A.]]
[[Category: Fromont, C.]]
[[Category: Hubbard, R.E.]]
[[Category: Massey, A.]]
[[Category: Sharp, S.]]
[[Category: Sheridan, L.]]
[[Category: Surgenor, A.]]
[[Category: Workman, P.]]
[[Category: Wright, L.]]
[[Category: PU6]]
[[Category: atp-binding]]
[[Category: atpase]]
[[Category: chaperone]]
[[Category: heat shock]]
[[Category: hsp90]]
[[Category: pu6]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Oct 29 18:44:10 2007''