PDBsum entry 1y8g

Signaling protein,transferase

PDB id: 1y8g

Contents

Protein chains

302 a.a. *

Waters ×158

* Residue conservation analysis

PDB id:

1y8g

Name:

Signaling protein,transferase

Title:

Catalytic and ubiqutin-associated domains of mark2/par-1: inactive double mutant with selenomethionine

Structure:

Map/microtubule affinity-regulating kinase 2. Chain: a, b. Fragment: catalytic and ubiquitin-associated domains, residues 39- 364. Synonym: par-1. Kin1. Serine/threonine kinase emk. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: mark2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.50Å R-factor: 0.201 R-free: 0.268

Authors:

S.Panneerselvam,A.Marx,E.-M.Mandelkow,E.Mandelkow

Key ref:

S.Panneerselvam et al. (2006). Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1. Structure, 14, 173-183. PubMed id: 16472737 DOI: 10.1016/j.str.2005.09.022

Date:

12-Dec-04 Release date: 14-Feb-06

Protein chains

O08679  (MARK2_RAT) -  Serine/threonine-protein kinase MARK2 from Rattus norvegicus

Seq: 722 a.a.

Struc: 302 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
• Enzyme class 3: E.C.2.7.11.26 - [tau protein] kinase.
• Reaction:
  1. L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H⁺
  2. L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2005.09.022

Structure 14:173-183 (2006)

PubMed id: 16472737

Structure of the catalytic and ubiquitin-associated domains of the protein kinase MARK/Par-1.

S.Panneerselvam, A.Marx, E.M.Mandelkow, E.Mandelkow.

ABSTRACT

The Ser/Thr kinase MARK2 phosphorylates tau protein at sites that cause detachment from microtubules in Alzheimer neurofibrillary degeneration. Homologs of MARK2 include Par-1 in C. elegans and Drosophila, which generates embryonic polarity. We report the X-ray structure of the catalytic and ubiquitin-associated domains (UBA) of human MARK2. The activity was altered by mutations in the ATP binding site and/or activation loop. The catalytic domain shows the small and large lobes typical of kinases. The substrate cleft is in an inactive, open conformation in the inactivated and the wild-type structure. The UBA domain is attached via a taut linker to the large lobe of the kinase domain and leans against a hydrophobic patch on the small lobe. The UBA structure is unusual because the orientation of its third helix is inverted, relative to previous structures. Possible implications of the structure for the regulation of kinase activity are discussed.

Selected figure(s)

Figure 7.
Figure 7. Common Docking Domain and ED Site of MAP Kinases Compared to MARK2
The structures of (A) MARK2 and (B) ERK2 (PDB code 2ERK [Canagarajah et al., 1997]) are shown in the same orientations after least-squares superposition of 35 residues from helix E to the catalytic loop. The common docking domain (CD, in red) according to Tanoue and Nishida (2003) is C terminal to the kinase domain and corresponds in MARK to the first half of the tether connecting the kinase domain to the UBA domain (residues vert, similar 305-315). The C-terminal extensions following the CD domain (linker and UBA domain in MARK2) are shown in purple. Characteristic for the CD domain is a cluster of negatively charged residues exposed to the surface, located in a bulge at the end of the catalytic domain (stick model representation).

The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 173-183) copyright 2006.

Figure was selected by an automated process.