PDBsum entry 2ac5

Transferase

PDB id: 2ac5

Contents

Protein chain

276 a.a. *

Metals

_ZN

Waters ×18

* Residue conservation analysis

PDB id:

2ac5

Name:

Transferase

Title:

Structure of human mnk2 kinase domain mutant d228g

Structure:

Map kinase-interacting serine/threonine kinase 2. Chain: a. Fragment: residues 70-385. Synonym: map kinase signal-integrating kinase 2, mnk2. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PQS)

Resolution:

3.20Å R-factor: 0.238 R-free: 0.306

Authors:

R.Jauch,M.C.Wahl,S.Jakel,K.Schreiter,B.Aicher,H.Jackle

Key ref:

R.Jauch et al. (2005). Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Structure, 13, 1559-1568. PubMed id: 16216586

Date:

18-Jul-05 Release date: 04-Oct-05

Protein chain

Q9HBH9  (MKNK2_HUMAN) -  MAP kinase-interacting serine/threonine-protein kinase 2 from Homo sapiens

Seq: 465 a.a.

Struc: 276 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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

Structure 13:1559-1568 (2005)

PubMed id: 16216586

Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site.

R.Jauch, S.Jäkel, C.Netter, K.Schreiter, B.Aicher, H.Jäckle, M.C.Wahl.

ABSTRACT

Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) target the translational machinery by phosphorylation of the eukaryotic initiation factor 4E (eIF4E). Here, we present the 2.1 A crystal structure of a nonphosphorylated Mnk2 fragment that encompasses the kinase domain. The results show Mnk-specific features such as a zinc binding motif and an atypical open conformation of the activation segment. In addition, the ATP binding pocket contains an Asp-Phe-Asp (DFD) in place of the canonical magnesium binding Asp-Phe-Gly (DFG) motif. The phenylalanine of this motif sticks into the ATP binding pocket and blocks ATP binding as observed with inhibitor bound and, thus, inactive p38 kinase. Replacement of the DFD by the canonical DFG motif affects the conformation of Mnk2, but not ATP binding and kinase activity. The results suggest that the ATP binding pocket and the activation segment of Mnk2 require conformational switches to provide kinase activity.