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.


1m8d

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1m8d.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:1m8d.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1m8d| PDB=1m8d | SCENE= }}
{{STRUCTURE_1m8d| PDB=1m8d | SCENE= }}
-
'''inducible nitric oxide synthase with Chlorzoxazone bound'''
+
===inducible nitric oxide synthase with Chlorzoxazone bound===
-
==Overview==
+
<!--
-
Nitric oxide is a key signaling molecule in many biological processes, making regulation of nitric oxide levels highly desirable for human medicine and for advancing our understanding of basic physiology. Designing inhibitors to specifically target one of the three nitric oxide synthase (NOS) isozymes that form nitric oxide from the L-Arg substrate poses a significant challenge due to the overwhelmingly conserved active sites. We report here 10 new X-ray crystallographic structures of inducible and endothelial NOS oxygenase domains cocrystallized with chlorzoxazone and four nitroindazoles: 5-nitroindazole, 6-nitroindazole, 7-nitroindazole, and 3-bromo-7-nitroindazole. Each of these bicyclic aromatic inhibitors has only one hydrogen bond donor and therefore cannot form the bidentate hydrogen bonds that the L-Arg substrate makes with Glu371. Instead, all of these inhibitors induce a conformational change in Glu371, creating an active site with altered molecular recognition properties. The cost of this conformational change is approximately 1-2 kcal, based on our measured constants for inhibitor binding to the wild-type and E371A mutant proteins. These inhibitors derive affinity by pi-stacking above the heme and replacing both intramolecular (Glu371-Met368) and intermolecular (substrate-Trp366) hydrogen bonds to the beta-sheet architecture underlying the active site. When bound to NOS, high-affinity inhibitors in this class are planar, whereas weaker inhibitors are nonplanar. Isozyme differences were observed in the pterin cofactor site, the heme propionate, and inhibitor positions. Computational docking predictions match the crystallographic results, including the Glu371 conformational change and inhibitor-binding orientations, and support a combined crystallographic and computational approach to isozyme-specific NOS inhibitor analysis and design.
+
The line below this paragraph, {{ABSTRACT_PUBMED_12437348}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 12437348 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_12437348}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Wallace, A V.]]
[[Category: Wallace, A V.]]
[[Category: Inhibitor-induced conformational change]]
[[Category: Inhibitor-induced conformational change]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:45:24 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:25:48 2008''

Revision as of 20:25, 2 July 2008

Image:1m8d.png

Template:STRUCTURE 1m8d

inducible nitric oxide synthase with Chlorzoxazone bound

Template:ABSTRACT PUBMED 12437348

About this Structure

1M8D is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency., Rosenfeld RJ, Garcin ED, Panda K, Andersson G, Aberg A, Wallace AV, Morris GM, Olson AJ, Stuehr DJ, Tainer JA, Getzoff ED, Biochemistry. 2002 Nov 26;41(47):13915-25. PMID:12437348

Page seeded by OCA on Wed Jul 2 23:25:48 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1m8d"
Personal tools