2hak

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PDB ID 2hak

Drag the structure with the mouse to rotate
, resolution 2.600Å
Gene: MARK1 (Homo sapiens)
Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Related: 1ZMU, 1ZMV, 1ZMW, 1Y8G


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



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. 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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