PDBsum entry 1cm8

Transferase

PDB id: 1cm8

Contents

Protein chain

329 a.a. *

Ligands

ANP ×2

Metals

_MG ×4

Waters ×186

* Residue conservation analysis

PDB id:

1cm8

Name:

Transferase

Title:

Phosphorylated map kinase p38-gamma

Structure:

Phosphorylated map kinase p38-gamma. Chain: a, b. Synonym: stress-activated protein kinase-3, erk6, erk5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.40Å R-factor: 0.232 R-free: 0.283

Authors:

S.Bellon,M.J.Fitzgibbon,T.Fox,H.M.Hsiao,K.P.Wilson

Key ref:

S.Bellon et al. (1999). The structure of phosphorylated p38gamma is monomeric and reveals a conserved activation-loop conformation. Structure Fold Des, 7, 1057-1065. PubMed id: 10508788 DOI: 10.1016/S0969-2126(99)80173-7

Date:

17-May-99 Release date: 17-May-00

Protein chains

P53778  (MK12_HUMAN) -  Mitogen-activated protein kinase 12 from Homo sapiens

Seq: 367 a.a.

Struc: 329 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.7.11.24 - mitogen-activated 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(+)

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

reference

DOI no: 10.1016/S0969-2126(99)80173-7

Structure Fold Des 7:1057-1065 (1999)

PubMed id: 10508788

The structure of phosphorylated p38gamma is monomeric and reveals a conserved activation-loop conformation.

S.Bellon, M.J.Fitzgibbon, T.Fox, H.M.Hsiao, K.P.Wilson.

ABSTRACT

BACKGROUND: Mitogen-activated protein (MAP) kinases mediate the cellular response to stimuli such as pro-inflammatory cytokines and environmental stress. P38gamma is a new member of the MAP kinase family, and is expressed at its highest levels in skeletal muscle. P38gamma is 63% identical in sequence to P38alpha. The structure of P38alpha MAP kinase has been determined in the apo, unphosphorylated, inactive form. The structures of apo unphosphorylated ERK2, a related MAP kinase, and apo phosphorylated ERK2 have also been determined. RESULTS: We have determined the structure of doubly phosphorylated P38gamma in complex with an ATP analog by X-ray crystallography. This is the first report of a structure of an activated kinase in the P38 subfamily, and the first bound to a nucleotide. P38gamma residue phosphoryl-Thr183 forms hydrogen bonds with five basic amino acids, and these interactions induce an interdomain rotation. The conformation of the activation loop of P38gamma is almost identical to that observed in the structure of activated ERK2. However, unlike ERK2, the crystal structure and solution studies indicate that activated P38gamma exists as a monomer. CONCLUSIONS: Interactions mediated by phosphoryl-Thr183 induce structural changes that direct the domains and active-site residues of P38gamma into a conformation consistent with catalytic activity. The conformation of the phosphorylation loop is likely to be similar in all activated MAP kinases, but not all activated MAP kinases form dimers.

Selected figure(s)

Figure 4.
Figure 4. Stereoview of AMP-PNP. All major interactions with protein sidechains are indicated by dashed gray lines. The bound Mg2+ ions are indicated by black spheres. The phosphate atoms are shown in purple. Met109 can be seen behind the adenine base, blocking the hydrophobic pocket. Water molecules have been removed for clarity.

The above figure is reprinted by permission from Cell Press: Structure Fold Des (1999, 7, 1057-1065) copyright 1999.

Figure was selected by an automated process.