1u32
From Proteopedia
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| - | [[Image:1u32.gif|left|200px]] | + | [[Image:1u32.gif|left|200px]] |
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| - | '''Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid''' | + | {{Structure |
| + | |PDB= 1u32 |SIZE=350|CAPTION= <scene name='initialview01'>1u32</scene>, resolution 2.00Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OKA:OKADAIC+ACID'>OKA</scene> and <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= PPP1CC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1U32 is a [ | + | 1U32 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U32 OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding., Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF, J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. PMID:[http:// | + | Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding., Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF, J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15280359 15280359] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phosphoprotein phosphatase]] | [[Category: Phosphoprotein phosphatase]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:26:41 2008'' |
Revision as of 12:26, 20 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Gene: | PPP1CC (Homo sapiens) | ||||||
| Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid
Overview
Protein phosphatase-1 and protein phosphatase-2B (calcineurin) are eukaryotic serine/threonine phosphatases that share 40% sequence identity in their catalytic subunits. Despite the similarities in sequence, these phosphatases are widely divergent when it comes to inhibition by natural product toxins, such as microcystin-LR and okadaic acid. The most prominent region of non-conserved sequence between these phosphatases corresponds to the beta12-beta13 loop of protein phosphatase-1, and the L7 loop of toxin-resistant calcineurin. In the present study, mutagenesis of residues 273-277 of the beta12-beta13 loop of the protein phosphatase-1 catalytic subunit (PP-1c) to the corresponding residues in calcineurin (312-316), resulted in a chimeric mutant that showed a decrease in sensitivity to microcystin-LR, okadaic acid, and the endogenous PP-1c inhibitor protein inhibitor-2. A crystal structure of the chimeric mutant in complex with okadaic acid was determined to 2.0-A resolution. The beta12-beta13 loop region of the mutant superimposes closely with that of wild-type PP-1c bound to okadaic acid. Systematic mutation of each residue in the beta12-beta13 loop of PP-1c showed that a single amino acid change (C273L) was the most influential in mediating sensitivity of PP-1c to toxins. Taken together, these data indicate that it is an individual amino acid residue substitution and not a change in the overall beta12-beta13 loop conformation of protein phosphatase-1 that contributes to disrupting important interactions with inhibitors such as microcystin-LR and okadaic acid.
About this Structure
1U32 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure and mutagenesis of a protein phosphatase-1:calcineurin hybrid elucidate the role of the beta12-beta13 loop in inhibitor binding., Maynes JT, Perreault KR, Cherney MM, Luu HA, James MN, Holmes CF, J Biol Chem. 2004 Oct 8;279(41):43198-206. Epub 2004 Jul 26. PMID:15280359
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