2clq

File:2clq.gif

spinqualitylabelsall models PDB ID 2clq Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.30Å
Sites:	and
Ligands:
Activity:	Mitogen-activated protein kinase kinase kinase, with EC number 2.7.11.25
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

STRUCTURE OF MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 5

OverviewOverview

Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases. Here, we present the structure of the human ASK1 catalytic domain in complex with staurosporine. Analytical ultracentrifugation (AUC) and crystallographic analysis showed that ASK1 forms a tight dimer (K(d) approximately 0.2 microM) interacting in a head-to-tail fashion. We found that the ASK1 phosphorylation motifs differ from known ASK1 phosphorylation sites but correspond well to autophosphorylation sites identified by mass spectrometry. Reporter gene assays showed that all three identified in vitro autophosphorylation sites (Thr813, Thr838, Thr842) regulate ASK1 signaling, but site-directed mutants showed catalytic activities similar to wild-type ASK1, suggesting a regulatory mechanism independent of ASK1 kinase activity. The determined high-resolution structure of ASK1 and identified ATP mimetic inhibitors will provide a first starting point for the further development of selective inhibitors.

About this StructureAbout this Structure

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

ReferenceReference

Structural and functional characterization of the human protein kinase ASK1., Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Muller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE, Knapp S, Structure. 2007 Oct;15(10):1215-26. PMID:17937911

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