1a9u: Difference between revisions

Revision as of 16:27, 30 June 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1a9u.png

1a9u, resolution 2.50Å ()

Ligands:

Structural annotation:
Resources:	CATH : 1A9U001, 1A9U002 InterPro : Ipr003527, Ipr008352, Ipr002290, Ipr008271, Ipr000719, Ipr011009 Pfam : PF00069 SCOP : d1a9u__ UniProt : Q16539

Functional annotation:
Cellular component:	cytoplasm nucleus
Biological process:	protein amino acid phosphorylation protein kinase cascade cell surface receptor linked signal transduction cell motility response to stress chemotaxis signal transduction
Molecular function:	protein kinase activity MP kinase activity transferase activity nucleotide binding MAP kinase kinase activity protein binding kinase activity ATP binding MAP kinase activity protein serine/threonine kinase activity

Evolutionary conservation:

Toggle Conservation Colors:	Rows = identical sequences:
Further Information:	Caveats, Explanation, Complete Results at ConSurfDB

Resources:

FirstGlance, OCA, PDBsum, RCSB

Coordinates:

save as pdb, mmCIF, xml

THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580

Template:ABSTRACT PUBMED 9753691

About this StructureAbout this Structure

1A9U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 16:27:08 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580'''
+===THE COMPLEX STRUCTURE OF THE MAP KINASE P38/SB203580===
-==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.
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+{{ABSTRACT_PUBMED_9753691}}
 ==About this Structure==
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 [[Category: Serine/threonine-protein kinase]]
 [[Category: Transferase]]
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