PDBsum entry 4bfm

Transferase

PDB id: 4bfm

Contents

Protein chain

313 a.a.

Ligands

ANP

SO4 ×6

Waters ×82

PDB id:

4bfm

Name:

Transferase

Title:

The crystal structure of mouse pk38

Structure:

Maternal embryonic leucine zipper kinase. Chain: a. Synonym: protein kinase pk38, mpk38, tyrosine-protein kinase melk. Engineered: yes. Mutation: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.35Å R-factor: 0.177 R-free: 0.208

Authors:

J.H.Yoo,Y.S.Cho,S.M.Park,H.S.Cho

Key ref:

Y.S.Cho et al. (2014). The structures of the kinase domain and UBA domain of MPK38 suggest the activation mechanism for kinase activity. Acta Crystallogr D Biol Crystallogr, 70, 514-521. PubMed id: 24531485 DOI: 10.1107/S1399004713027806

Date:

21-Mar-13 Release date: 12-Feb-14

Protein chain

Q61846  (MELK_MOUSE) -  Maternal embryonic leucine zipper kinase from Mus musculus

Seq: 643 a.a.

Struc: 313 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

• Enzyme class 3: 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⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + 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: 10.1107/S1399004713027806

Acta Crystallogr D Biol Crystallogr 70:514-521 (2014)

PubMed id: 24531485

The structures of the kinase domain and UBA domain of MPK38 suggest the activation mechanism for kinase activity.

Y.S.Cho, J.Yoo, S.Park, H.S.Cho.

ABSTRACT

Murine protein serine/threonine kinase 38 (MPK38) is the murine orthologue of human maternal embryonic leucine-zipper kinase (MELK), which belongs to the SNF1/AMPK family. MELK is considered to be a promising drug target for anticancer therapy because overexpression and hyperactivation of MELK is correlated with several human cancers. Activation of MPK38 requires the extended sequence (ExS) containing the ubiquitin-associated (UBA) linker and UBA domain and phosphorylation of the activation loop. However, the activation mechanism of MPK38 is unknown. This paper reports the crystal structure of MPK38 (T167E), which mimics a phosphorylated state of the activation loop, in complex with AMP-PNP. In the MPK38 structure, the UBA linker forces an inward movement of the αC helix. Phosphorylation of the activation loop then induces movement of the activation loop towards the C-lobe and results in interlobar cleft closure. These processes generate a fully active state of MPK38. This structure suggests that MPK38 has a similar molecular mechanism regulating activation as in other kinases of the SNF1/AMPK family.