1jk7: Difference between revisions

Revision as of 21:19, 2 May 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. 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 Fri May 2 21:19:22 2008

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OCA

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 [[Image:1jk7.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1jk7 |SIZE=350|CAPTION= <scene name='initialview01'>1jk7</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_1jk7", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OKA:OKADAIC+ACID'>OKA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1jk7|  PDB=1jk7  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jk7 OCA], [http://www.ebi.ac.uk/pdbsum/1jk7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jk7 RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF THE TUMOR-PROMOTER OKADAIC ACID BOUND TO PROTEIN PHOSPHATASE-1'''
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 [[Category: James, M N.]]
 [[Category: Maynes, J T.]]
-[[Category: hydrolase-inhibitor complex]]
+[[Category: Hydrolase-inhibitor complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 21:19:22 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:34:52 2008''