PDBsum entry: 1jk7

Hydrolase/toxin

PDB id: 1jk7

Contents

Protein chain

294 a.a. *

Ligands

SO4

OKA

BME ×3

Metals

_MN ×2

Waters ×178

* Residue conservation analysis

PDB id:

1jk7

Name:

Hydrolase/toxin

Title:

Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1

Structure:

Serine/threonine protein phosphatase pp1-gamma catalytic subunit. Chain: a. Synonym: pp-1g. Engineered: yes

Source:

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

Resolution:

1.90Å R-factor: 0.199 R-free: 0.225

Authors:

J.T.Maynes,K.S.Bateman,M.M.Cherney,A.K.Das,M.N.James

Key ref:

J.T.Maynes et al. (2001). Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1. J Biol Chem, 276, 44078-44082. PubMed id: 11535607 DOI: 10.1074/jbc.M107656200

Date:

11-Jul-01 Release date: 15-Aug-01

Protein chain

P36873  (PP1G_HUMAN) -  Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

Seq: 323 a.a.

Struc: 294 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.16 - Phosphoprotein phosphatase.
• Reaction: A phosphoprotein + H₂O = a protein + phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: protein complex (10 terms)
• Biological process: cell cycle (4 terms)
• Biochemical function: protein binding (6 terms)

Added reference

DOI no: 10.1074/jbc.M107656200

J Biol Chem 276:44078-44082 (2001)

PubMed id: 11535607

Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1.

J.T.Maynes, K.S.Bateman, M.M.Cherney, A.K.Das, H.A.Luu, C.F.Holmes, M.N.James.

ABSTRACT

Protein phosphatase-1 (PP1) plays a key role in dephosphorylation in numerous biological processes such as glycogen metabolism, cell cycle regulation, smooth muscle contraction, and protein synthesis. Microorganisms produce a variety of inhibitors of PP1, which include the microcystin class of inhibitors and okadaic acid, the latter being the major cause of diarrhetic shellfish poisoning and a powerful tumor promoter. We have determined the crystal structure of the molecular complex of okadaic acid bound to PP1 to a resolution of 1.9 A. This structure reveals that the acid binds in a hydrophobic groove adjacent to the active site of the protein and interacts with basic residues within the active site. Okadaic acid exhibits a cyclic structure, which is maintained via an intramolecular hydrogen bond. This is reminiscent of other macrocyclic protein phosphatase inhibitors. The inhibitor-bound enzyme shows very little conformational change when compared with two other PP1 structures, except in the inhibitor-sensitive beta12-beta13 loop region. The selectivity of okadaic acid for protein phosphatases-1 and -2A but not PP-2B (calcineurin) may be reassessed in light of this study.

Selected figure(s)

Figure 1.
Fig. 1. A, architecture of the PP1·OA complex with the protein shown as a ribbon representation, coloring is blue at the N terminus to red at the carboxyl terminus. OA is shown as ball-and-sticks with carbon atoms in yellow and oxygen atoms in red. The two manganese atoms in the active site are shown as yellow spheres. B, electron density map of OA bound to PP1. The protein is shown as a space-filling model, and OA is as in A. The map is a 2F[o]-F[c]-simulated annealing omit map generated in CNS (13) where the inhibitor was omitted in the map calculation. Map is contoured at 1.5 , d[min] = 1.9 Å. All figures except 1B were generated using the programs MOLSCRIPT (34), BOBSCRIPT (35), GRASP (36) and RASTER3D (7).

Figure 2.
Fig. 2. A, stereo representation of the active site of the PP1·OA complex. Pertinent active site residues are labeled and are shown as a ball-and-stick representation with carbon atoms colored gray, oxygen atoms colored red, and nitrogen atoms colored blue. OA is shown as a ball-and-stick representation with carbon atoms colored yellow and oxygen atoms colored red. The intramolecular hydrogen bond in OA is shown as a dashed line. The active-site manganese atoms are shown as yellow spheres. B, active site of the PP1·OA complex. All residues of PP1 within 4 Å of the OA are shown, the closest residue-OA interactions are shown by dashed lines, and the distances of all possible hydrogen bonding interactions are labeled.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 44078-44082) copyright 2001.

Figures were selected by an automated process.