PMID- 10048930
OWN - NLM
STAT- MEDLINE
DCOM- 19990225
LR  - 20131121
IS  - 1072-8368 (Print)
IS  - 1072-8368 (Linking)
VI  - 6
IP  - 2
DP  - 1999 Feb
TI  - Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications
      for regulated activation.
PG  - 174-81
AB  - The crystal structure of the catalytic domain from the MAPK phosphatase Pyst1
      (Pyst1-CD) has been determined at 2.35 A. The structure adopts a protein tyrosine
      phosphatase (PTPase) fold with a shallow active site that displays a distorted
      geometry in the absence of its substrate with some similarity to the
      dual-specificity phosphatase cdc25. Functional characterization of Pyst1-CD
      indicates it is sufficient to dephosphorylate activated ERK2 in vitro. Kinetic
      analysis of Pyst1 and Pyst1-CD using the substrate p-nitrophenyl phosphate (pNPP)
      reveals that both molecules undergo catalytic activation in the presence of
      recombinant inactive ERK2, switching from a low- to high-activity form. Mutation 
      of Asp 262, located 5.5 A distal to the active site, demonstrates it is essential
      for catalysis in the high-activity ERK2-dependent conformation of Pyst1 but not
      for the low-activity ERK2-independent form, suggesting that ERK2 induces closure 
      of the Asp 262 loop over the active site, thereby enhancing Pyst1 catalytic
      efficiency.
FAU - Stewart, A E
AU  - Stewart AE
AD  - Structural Biology Laboratory, Imperial Cancer Research Fund, London, UK.
FAU - Dowd, S
AU  - Dowd S
FAU - Keyse, S M
AU  - Keyse SM
FAU - McDonald, N Q
AU  - McDonald NQ
LA  - eng
SI  - PDB/1MKP
PT  - Journal Article
PL  - United States
TA  - Nat Struct Biol
JT  - Nature structural biology
JID - 9421566
RN  - 0 (Recombinant Proteins)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Aspartic Acid/metabolism
MH  - Binding Sites
MH  - Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Dual Specificity Phosphatase 6
MH  - Molecular Sequence Data
MH  - Protein Conformation
MH  - Protein Tyrosine Phosphatases/*chemistry/metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Homology, Amino Acid
EDAT- 1999/02/27 03:15
MHDA- 2001/03/23 10:01
CRDT- 1999/02/27 03:15
PHST- 1999/02/27 03:15 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/02/27 03:15 [entrez]
AID - 10.1038/5861 [doi]
PST - ppublish
SO  - Nat Struct Biol. 1999 Feb;6(2):174-81. doi: 10.1038/5861.