2hak
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(New page: 200px<br /> <applet load="2hak" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hak, resolution 2.600Å" /> '''Catalytic and ubiq...)
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Revision as of 20:22, 12 November 2007
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Catalytic and ubiqutin-associated domains of MARK1/PAR-1
Overview
The microtubule-associated protein (MAP)/microtubule affinity regulating, kinase (MARK)/Par-1 phosphorylates microtubule-associated proteins tau, MAP2, and MAP4 and is involved in the regulation of microtubule-based, transport. Par-1, a homologue of MARK in Drosophila and Caenorhabditis, elegans, is essential for the development of embryonic polarity. Four, isoforms of MARK are found in humans. Recently, we reported the crystal, structure of the catalytic and ubiquitin-associated domains of MARK2, an, isoform enriched in brain (Panneerselvam, S., Marx, A., Mandelkow, E.-M., and Mandelkow, E. (2006) Structure 14, 173-183). It showed that the, ubiquitin-associated domain (UBA) domain has an unusual fold and binds to, the N-terminal lobe of the catalytic domain. This is at variance with a, previous low resolution structure derived from small angle solution, scattering (Jaleel, M., Villa, F., Deak, M., Toth, R., Prescott, A. R., Van Aalten, D. M., and Alessi, D. R. (2006) Biochem. J. 394, 545-555), which predicts binding of the UBA domain to the larger, C-terminal lobe., Here we report the crystal structure of the catalytic and UBA domain of, another isoform, MARK1. Although the crystal packing of the two isoforms, are unrelated, the overall conformations of the molecules are similar., Notably, the UBA domain has the same unusual conformation as in MARK2, and, it binds at the same site. Remarkable differences occur in the catalytic, domain at helix C, the catalytic loop, and the activation segment.
About this Structure
2HAK is a Single protein structure of sequence from Homo sapiens. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2., Marx A, Nugoor C, Muller J, Panneerselvam S, Timm T, Bilang M, Mylonas E, Svergun DI, Mandelkow EM, Mandelkow E, J Biol Chem. 2006 Sep 15;281(37):27586-99. Epub 2006 Jun 27. PMID:16803889
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