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1jk7
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Protein phosphatase-1 (PP1) plays a key role in dephosphorylation in | + | 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 Structure== | ==About this Structure== | ||
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[[Category: Phosphoprotein phosphatase]] | [[Category: Phosphoprotein phosphatase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bateman, K | + | [[Category: Bateman, K S.]] |
| - | [[Category: Cherney, M | + | [[Category: Cherney, M M.]] |
| - | [[Category: Das, A | + | [[Category: Das, A K.]] |
| - | [[Category: James, M | + | [[Category: James, M N.]] |
| - | [[Category: Maynes, J | + | [[Category: Maynes, J T.]] |
[[Category: BME]] | [[Category: BME]] | ||
[[Category: MN]] | [[Category: MN]] | ||
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[[Category: hydrolase-inhibitor complex]] | [[Category: hydrolase-inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:23:34 2008'' |
Revision as of 11:23, 21 February 2008
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CRYSTAL STRUCTURE OF THE TUMOR-PROMOTER OKADAIC ACID BOUND TO PROTEIN PHOSPHATASE-1
Overview
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 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.
Reference
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
Page seeded by OCA on Thu Feb 21 13:23:34 2008
