1jk7: Difference between revisions

Revision as of 14:23, 21 February 2008

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

Page seeded by OCA on Thu Feb 21 13:23:34 2008

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OCA

@@ Line 4: / Line 4: @@
 ==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.
+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==
@@ Line 14: / Line 14: @@
 [[Category: Phosphoprotein phosphatase]]
 [[Category: Single protein]]
-[[Category: Bateman, K.S.]]
+[[Category: Bateman, K S.]]
-[[Category: Cherney, M.M.]]
+[[Category: Cherney, M M.]]
-[[Category: Das, A.K.]]
+[[Category: Das, A K.]]
-[[Category: James, M.N.]]
+[[Category: James, M N.]]
-[[Category: Maynes, J.T.]]
+[[Category: Maynes, J T.]]
 [[Category: BME]]
 [[Category: MN]]
@@ Line 25: / Line 25: @@
 [[Category: hydrolase-inhibitor complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:07:46 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:23:34 2008''