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.


1bl6

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1bl6.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1bl6.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1bl6| PDB=1bl6 | SCENE= }}
{{STRUCTURE_1bl6| PDB=1bl6 | SCENE= }}
-
'''THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB216995'''
+
===THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB216995===
-
==Overview==
+
<!--
-
BACKGROUND: The mitogen-activated protein (MAP) kinases are important signaling molecules that participate in diverse cellular events and are potential targets for intervention in inflammation, cancer, and other diseases. The MAP kinase p38 is responsive to environmental stresses and is involved in the production of cytokines during inflammation. In contrast, the activation of the MAP kinase ERK2 (extracellular-signal-regulated kinase 2) leads to cellular differentiation or proliferation. The anti-inflammatory agent pyridinylimidazole and its analogs (SB [SmithKline Beecham] compounds) are highly potent and selective inhibitors of p38, but not of the closely-related ERK2, or other serine/threonine kinases. Although these compounds are known to bind to the ATP-binding site, the origin of the inhibitory specificity toward p38 is not clear. RESULTS: We report the structural basis for the exceptional selectivity of these SB compounds for p38 over ERK2, as determined by comparative crystallography. In addition, structural data on the origin of olomoucine (a better inhibitor of ERK2) selectivity are presented. The crystal structures of four SB compounds in complex with p38 and of one SB compound and olomoucine in complex with ERK2 are presented here. The SB inhibitors bind in an extended pocket in the active site and are complementary to the open domain structure of the low-activity form of p38. The relatively closed domain structure of ERK2 is able to accommodate the smaller olomoucine. CONCLUSIONS: The unique kinase-inhibitor interactions observed in these complexes originate from amino-acid replacements in the active site and replacements distant from the active site that affect the size of the domain interface. This structural information should facilitate the design of better MAP-kinase inhibitors for the treatment of inflammation and other diseases.
+
The line below this paragraph, {{ABSTRACT_PUBMED_9753691}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 9753691 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_9753691}}
==About this Structure==
==About this Structure==
Line 36: Line 40:
[[Category: Serine/ threonine-protein kinase]]
[[Category: Serine/ threonine-protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:39:22 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:20:00 2008''

Revision as of 16:20, 30 June 2008

Image:1bl6.png

Template:STRUCTURE 1bl6

THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB216995

Template:ABSTRACT PUBMED 9753691

About this Structure

1BL6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis of inhibitor selectivity in MAP kinases., Wang Z, Canagarajah BJ, Boehm JC, Kassisa S, Cobb MH, Young PR, Abdel-Meguid S, Adams JL, Goldsmith EJ, Structure. 1998 Sep 15;6(9):1117-28. PMID:9753691

Page seeded by OCA on Mon Jun 30 19:20:00 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bl6"
Personal tools