1jk7
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CRYSTAL STRUCTURE OF THE TUMOR-PROMOTER OKADAIC ACID BOUND TO PROTEIN PHOSPHATASE-1
OverviewOverview
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.
About this StructureAbout this Structure
1JK7 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1., Maynes JT, Bateman KS, Cherney MM, Das AK, Luu HA, Holmes CF, James MN, J Biol Chem. 2001 Nov 23;276(47):44078-82. Epub 2001 Sep 4. PMID:11535607
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