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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''' | '''Crystal structure of a Protein Phosphatase-1: Calcineurin Hybrid Bound to Okadaic Acid''' | ||
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[[Category: Maynes, J T.]] | [[Category: Maynes, J T.]] | ||
[[Category: Perreault, K R.]] | [[Category: Perreault, K R.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:41:53 2008'' | |
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Revision as of 07:41, 3 May 2008
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 Page seeded by OCA on Sat May 3 10:41:53 2008
