1JK7

CRYSTAL STRUCTURE OF THE TUMOR-PROMOTER OKADAIC ACID BOUND TO PROTEIN PHOSPHATASE-1

Summary for 1JK7

• Entry DOI: 10.2210/pdb1jk7/pdb
• Descriptor: SERINE/THREONINE PROTEIN PHOSPHATASE PP1-GAMMA CATALYTIC SUBUNIT, MANGANESE (II) ION, SULFATE ION, ... (6 entities in total)
• Functional Keywords: hydrolase-inhibitor complex, hydrolase-toxin complex, hydrolase/toxin
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P36873
• Total number of polymer chains: 1
• Total formula weight: 38276.12

Authors

Maynes, J.T.,Bateman, K.S.,Cherney, M.M.,Das, A.K.,James, M.N. (deposition date: 2001-07-11, release date: 2001-08-15, Last modification date: 2023-08-16)

Primary citation

Maynes, J.T.,Bateman, K.S.,Cherney, M.M.,Das, A.K.,Luu, H.A.,Holmes, C.F.,James, M.N.
Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1.
J.Biol.Chem., 276:44078-44082, 2001

PubMed 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.

PubMed: 11535607
DOI: 10.1074/jbc.M107656200

Experimental method

X-RAY DIFFRACTION (1.9 Å)