1MKP

CRYSTAL STRUCTURE OF PYST1 (MKP3)

Summary for 1MKP

• Entry DOI: 10.2210/pdb1mkp/pdb
• Descriptor: PYST1, CHLORIDE ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (4 entities in total)
• Functional Keywords: hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q16828
• Total number of polymer chains: 1
• Total formula weight: 16428.28

Authors

Stewart, A.E.,Dowd, S.,Keyse, S.,Mcdonald, N.Q. (deposition date: 1998-07-11, release date: 1999-07-22, Last modification date: 2024-02-14)

Primary citation

Stewart, A.E.,Dowd, S.,Keyse, S.M.,McDonald, N.Q.
Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation.
Nat.Struct.Biol., 6:174-181, 1999

PubMed Abstract: 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.

PubMed: 10048930
DOI: 10.1038/5861

Experimental method

X-RAY DIFFRACTION (2.35 Å)