PDBsum entry 2vd5

Transferase

PDB id: 2vd5

Contents

Protein chains

390 a.a. *

Ligands

BI8 ×2

Waters ×9

* Residue conservation analysis

PDB id:

2vd5

Name:

Transferase

Title:

Structure of human myotonic dystrophy protein kinase in complex with the bisindoylmaleide inhibitor bim viii

Structure:

Dmpk protein. Chain: a, b. Fragment: kinase domain, residues 11-420. Synonym: myotonic dystrophy protein kinase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3-prare2.

Resolution:

2.80Å R-factor: 0.198 R-free: 0.244

Authors:

A.C.W.Pike,A.Amos,J.Elkins,A.Bullock,K.Guo,O.Fedorov,G.Bunkoczi, P.Filippakopoulos,E.S.Pilka,E.Ugochukwu,C.Umeano,F.Niesen, M.Sundstrom,J.Weigelt,A.Edwards,C.H.Arrowsmith,F.Von Delft,S.Knapp

Key ref:

J.M.Elkins et al. (2009). Structure of dystrophia myotonica protein kinase. Protein Sci, 18, 782-791. PubMed id: 19309729

Date:

30-Sep-07 Release date: 06-Nov-07

Protein chains

Q09013  (DMPK_HUMAN) -  Myotonin-protein kinase from Homo sapiens

Seq: 629 a.a.

Struc: 390 a.a.

Enzyme reactions

• Enzyme class: 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⁺

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

reference

Protein Sci 18:782-791 (2009)

PubMed id: 19309729

Structure of dystrophia myotonica protein kinase.

J.M.Elkins, A.Amos, F.H.Niesen, A.C.Pike, O.Fedorov, S.Knapp.

ABSTRACT

Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain involved in the multimerization. The crystal structure of the kinase domain of DMPK bound to the inhibitor bisindolylmaleimide VIII (BIM-8) revealed a dimeric enzyme associated by a conserved dimerization domain. The affinity of dimerisation suggested that the kinase domain alone is insufficient for dimerisation in vivo and that the coiled-coil domains are required for stable dimer formation. The kinase domain is in an active conformation, with a fully-ordered and correctly positioned alphaC helix, and catalytic residues in a conformation competent for catalysis. The conserved hydrophobic motif at the C-terminal extension of the kinase domain is bound to the N-terminal lobe of the kinase domain, despite being unphosphorylated. Differences in the arrangement of the C-terminal extension compared to the closely related Rho-associated kinases include an altered PXXP motif, a different conformation and binding arrangement for the turn motif, and a different location for the conserved NFD motif. The BIM-8 inhibitor occupies the ATP site and has similar binding mode as observed in PDK1.