This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2oow

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2oow.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2oow.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2oow| PDB=2oow | SCENE= }}
{{STRUCTURE_2oow| PDB=2oow | SCENE= }}
-
'''MIF Bound to a Fluorinated OXIM Derivative'''
+
===MIF Bound to a Fluorinated OXIM Derivative===
-
==Overview==
+
<!--
-
Pharmacophores are chemical scaffolds upon which changes in chemical moieties (R-groups) at specific sites are made to identify a combination of R-groups that increases the therapeutic potency of a small molecule inhibitor while minimizing adverse effects. We developed a pharmacophore based on a carbonyloxime (OXIM) scaffold for macrophage migration inhibitory factor (MIF), a protein involved in the pathology of sepsis, to validate that inhibition of a catalytic site could produce therapeutic benefits. We studied the crystal structures of MIF.OXIM-based inhibitors and found two opposite orientations for binding to the active site that were dependent on the chemical structures of an R-group. One orientation was completely unexpected based on previous studies with hydroxyphenylpyruvate and (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1). We further confirmed that the unexpected binding mode targets MIF in cellular studies by showing that one compound, OXIM-11, abolished the counter-regulatory activity of MIF on anti-inflammatory glucocorticoid action. OXIM-11 treatment of mice, initiated 24 h after the onset of cecal ligation and puncture-induced sepsis, significantly improved survival when compared with vehicle-treated controls, confirming that inhibition of the MIF catalytic site could produce therapeutic effects. The crystal structures of the MIF inhibitor complexes provide insight for further structure-based drug design efforts.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17526494}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17526494 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17526494}}
==Disease==
==Disease==
Line 31: Line 35:
[[Category: Alternative ligand-binding mode]]
[[Category: Alternative ligand-binding mode]]
[[Category: Isomerase]]
[[Category: Isomerase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:21:26 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:19:01 2008''

Revision as of 15:19, 27 July 2008

Image:2oow.png

Template:STRUCTURE 2oow

Contents

MIF Bound to a Fluorinated OXIM Derivative

Template:ABSTRACT PUBMED 17526494

Disease

Known disease associated with this structure: Persistent Mullerian duct syndrome, type I OMIM:[600957], Rheumatoid arthritis, systemic juvenile, susceptibility to OMIM:[153620]

About this Structure

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

Reference

Alternative chemical modifications reverse the binding orientation of a pharmacophore scaffold in the active site of macrophage migration inhibitory factor., Crichlow GV, Cheng KF, Dabideen D, Ochani M, Aljabari B, Pavlov VA, Miller EJ, Lolis E, Al-Abed Y, J Biol Chem. 2007 Aug 10;282(32):23089-95. Epub 2007 May 25. PMID:17526494

Page seeded by OCA on Sun Jul 27 18:19:01 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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