PMID- 10508788
OWN - NLM
STAT- MEDLINE
DCOM- 19991215
LR  - 20190915
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 9
DP  - 1999 Sep 15
TI  - The structure of phosphorylated p38gamma is monomeric and reveals a conserved
      activation-loop conformation.
PG  - 1057-65
AB  - 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.
FAU - Bellon, S
AU  - Bellon S
AD  - Vertex Pharmaceuticals Incorporated 130 Waverly Street, Cambridge, MA 02139-4211,
      USA. bellon@vpharm.com.
FAU - Fitzgibbon, M J
AU  - Fitzgibbon MJ
FAU - Fox, T
AU  - Fox T
FAU - Hsiao, H M
AU  - Hsiao HM
FAU - Wilson, K P
AU  - Wilson KP
LA  - eng
SI  - PDB/1CM8
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 25612-73-1 (Adenylyl Imidodiphosphate)
RN  - 2ZD004190S (Threonine)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.7.1.- (Mitogen-Activated Protein Kinase 10)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - Adenylyl Imidodiphosphate/chemistry/metabolism
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Dimerization
MH  - Enzyme Activation
MH  - Magnesium/chemistry/metabolism
MH  - Methionine/chemistry/metabolism
MH  - Mitogen-Activated Protein Kinase 1/chemistry
MH  - Mitogen-Activated Protein Kinase 10
MH  - Mitogen-Activated Protein Kinases/*chemistry/*metabolism
MH  - Models, Molecular
MH  - Phosphorylation
MH  - Protein Conformation
MH  - Protein-Tyrosine Kinases/chemistry
MH  - Threonine/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/10/06 00:00
MHDA- 1999/10/06 00:01
CRDT- 1999/10/06 00:00
PHST- 1999/10/06 00:00 [pubmed]
PHST- 1999/10/06 00:01 [medline]
PHST- 1999/10/06 00:00 [entrez]
AID - st7913 [pii]
AID - 10.1016/s0969-2126(99)80173-7 [doi]
PST - ppublish
SO  - Structure. 1999 Sep 15;7(9):1057-65. doi: 10.1016/s0969-2126(99)80173-7.