We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

2ieh

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2ieh.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2ieh.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2ieh| PDB=2ieh | SCENE= }}
{{STRUCTURE_2ieh| PDB=2ieh | SCENE= }}
-
'''Crystal structure of human kinesin Eg5 in complex with (R)-mon97, a new monastrol-based inhibitor that binds as (R)-enantiomer'''
+
===Crystal structure of human kinesin Eg5 in complex with (R)-mon97, a new monastrol-based inhibitor that binds as (R)-enantiomer===
-
==Overview==
+
<!--
-
Drugs that target mitotic spindle proteins have been proven useful for tackling tumor growth. Eg5, a kinesin-5 family member, represents a potential target, since its inhibition leads to prolonged mitotic arrest through the activation of the mitotic checkpoint and apoptotic cell death. Monastrol, a specific dihydropyrimidine inhibitor of Eg5, shows stereo-specificity, since predominantly the (S)-, but not the (R)-, enantiomer has been shown to be the biologically active compound in vitro and in cell-based assays. Here, we solved the crystal structure (2.7A) of the complex between human Eg5 and a new keto derivative of monastrol (named mon-97), a potent antimitotic inhibitor. Surprisingly, we identified the (R)-enantiomer bound in the active site, and not, as for monastrol, the (S)-enantiomer. The absolute configuration of this more active (R)-enantiomer has been unambiguously determined via chemical correlation and x-ray analysis. Unexpectedly, both the R- and the S-forms inhibit Eg5 ATPase activity with IC(50) values of 110 and 520 nM (basal assays) and 150 nm and 650 nm (microtubule-stimulated assays), respectively. However, the difference was large enough for the protein to select the (R)- over the (S)-enantiomer. Taken together, these results show that in this new monastrol family, both (R)- and (S)-enantiomers can be active as Eg5 inhibitors. This considerably broadens the alternatives for rational drug design.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17251189}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17251189 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17251189}}
==About this Structure==
==About this Structure==
Line 28: Line 32:
[[Category: Flanked by three alpha-helices on each side]]
[[Category: Flanked by three alpha-helices on each side]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 14 11:38:22 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:45:39 2008''

Revision as of 20:45, 28 July 2008

Image:2ieh.png

Template:STRUCTURE 2ieh

Crystal structure of human kinesin Eg5 in complex with (R)-mon97, a new monastrol-based inhibitor that binds as (R)-enantiomer

Template:ABSTRACT PUBMED 17251189

About this Structure

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

Reference

Structure of human Eg5 in complex with a new monastrol-based inhibitor bound in the R configuration., Garcia-Saez I, DeBonis S, Lopez R, Trucco F, Rousseau B, Thuery P, Kozielski F, J Biol Chem. 2007 Mar 30;282(13):9740-7. Epub 2007 Jan 23. PMID:17251189

Page seeded by OCA on Mon Jul 28 23:45:39 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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