1xdg

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1xdg.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1xdg.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1xdg| PDB=1xdg | SCENE= }}
{{STRUCTURE_1xdg| PDB=1xdg | SCENE= }}
-
'''X-ray structure of LFA-1 I-domain in complex with LFA878 at 2.1A resolution'''
+
===X-ray structure of LFA-1 I-domain in complex with LFA878 at 2.1A resolution===
-
==Overview==
+
<!--
-
The integrin lymphocyte function-associated antigen-1 (LFA-1) (alphaLbeta2; CD11a/CD18) plays an important role in leukocyte migration and T cell activation. LFA-1 is inhibited by the cholesterol-lowering drug lovastatin, which binds to an allosteric site of the alphaL I domain termed the lovastatin site (L-site). Here we report for the first time the x-ray structures of the LFA-1 I domain complexed with derivatives of lovastatin optimized for LFA-1 inhibition. This analysis identified two new subpockets within the L-site occupied by chemical groups of the statin derivatives but not by lovastatin itself. Occupancy of these L-site subpockets led to distinct conformational changes in LFA-1, which were detectable by an epitope-monitoring assay. We utilized this assay to demonstrate improved LFA-1 inhibition in human blood in vitro and in blood samples from treated animals ex vivo. Moreover, we demonstrate that the novel lovastatin-derived LFA-1 inhibitor LFA878 exhibits potent anti-inflammatory effects in carrageenan-induced rat paw edema. In summary, the findings reported here extend the understanding of LFA-1 inhibition at the molecular level, allow for the identification and design of LFA-1 inhibitors of further enhanced potency, and support the expectation that LFA-1 inhibitors binding to the L-site will be of therapeutic value in treating inflammatory diseases.
+
The line below this paragraph, {{ABSTRACT_PUBMED_15304496}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 15304496 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_15304496}}
==About this Structure==
==About this Structure==
Line 28: Line 32:
[[Category: I-domain]]
[[Category: I-domain]]
[[Category: Rossman-fold]]
[[Category: Rossman-fold]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:53:17 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:04:15 2008''

Revision as of 08:04, 28 July 2008

Image:1xdg.png

Template:STRUCTURE 1xdg

X-ray structure of LFA-1 I-domain in complex with LFA878 at 2.1A resolution

Template:ABSTRACT PUBMED 15304496

About this Structure

1XDG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Improved lymphocyte function-associated antigen-1 (LFA-1) inhibition by statin derivatives: molecular basis determined by x-ray analysis and monitoring of LFA-1 conformational changes in vitro and ex vivo., Weitz-Schmidt G, Welzenbach K, Dawson J, Kallen J, J Biol Chem. 2004 Nov 5;279(45):46764-71. Epub 2004 Aug 10. PMID:15304496

Page seeded by OCA on Mon Jul 28 11:04:15 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xdg"
Personal tools