2fwy

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2fwy.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2fwy.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2fwy| PDB=2fwy | SCENE= }}
{{STRUCTURE_2fwy| PDB=2fwy | SCENE= }}
-
'''Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-H64'''
+
===Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-H64===
-
==Overview==
+
<!--
-
Hsp90 chaperones play a critical role in modulating the activity of many cell signaling proteins and are an attractive target for anti-cancer therapeutics. We report here the structures of the water soluble 8-aryl-sulfanyl adenine class Hsp90 inhibitors, 1 (PU-H71) and 2 (PU-H64), in complex with the N-terminal domain of human Hsp90alpha. The conformation of 1 when bound to Hsp90 differs from previously reported 8-aryl adenine Hsp90 inhibitors including 3 (PU24FCl). While the binding mode for 3 places the 2'-halide of the 8-aryl group on top of the adenine ring, for 1 and 2, we show that the 2'-halide is rotated approximately 180 degrees away. This difference explains the opposing trends in Hsp90 inhibitory activity for the 2'-halo derivatives of the 3',4',5'-trimethoxy series where Cl &gt; Br &gt; I compared to the 4',5'-methylenedioxy series where I &gt; Br &gt; Cl. We also present quantum chemical calculations of 2 and its analogues that illuminate their basis for Hsp90 inhibition. The calculated conformation of 2 agreed well with the crystallographically observed conformations of 1 and 2. The predictive nature of the calculations has allowed the exploration of additional derivatives based on the 8-aryl adenine scaffold.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16884307}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16884307 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16884307}}
==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Pu3]]
[[Category: Pu3]]
[[Category: Purine]]
[[Category: Purine]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:24:10 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:36:00 2008''

Revision as of 11:36, 29 July 2008

Image:2fwy.png

Template:STRUCTURE 2fwy

Structure of human Hsp90-alpha bound to the potent water soluble inhibitor PU-H64

Template:ABSTRACT PUBMED 16884307

About this Structure

2FWY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90 inhibitors., Immormino RM, Kang Y, Chiosis G, Gewirth DT, J Med Chem. 2006 Aug 10;49(16):4953-60. PMID:16884307

Page seeded by OCA on Tue Jul 29 14:36:00 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2fwy"
Personal tools