Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymes protein-carboxyl methylase and protein methylesterase reversibly modify the charge and structure of proteins by adding and removing methyl groups on free carboxyl groups of proteins. Since this posttranslational system has been implicated in biological processes that required calcium, the carboxyl methylation of calmodulin was investigated. Calmodulin was an excellent substrate for both protein-carboxyl methylase and protein methylesterase. Carboxyl methylation of calmodulin resulted in inactivation, since methylated calmodulin was less capable of activating cyclic nucleotide phosphodiesterase. To determine whether the carboxyl methylation of calmodulin was simply a test tube reaction or a biochemical reaction normally occurring in intact cells, two different cell lines were labeled with [methyl-3H]methionine. Calmodulin was isolated by affinity chromatography and was found to be carboxyl methylated. Finally, calcineurin was also an excellent substrate for the methylase, suggesting that other calcium-binding proteins may be affected by protein methylation-demethylation.
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PMID:Enzymatic carboxyl methylation of calcium-binding proteins. 631 68

Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes which have been purified, but not cloned. Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, we report that substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A and formation of stable complexes between PP2A and several cellular proteins. One of these cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from yeast to human and contains a motif found in lipases having a catalytic triad-activated serine as their active site nucleophile. Bacterially expressed PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 represents the first mammalian protein methylesterase to be cloned. Several lines of evidence indicate that, although there appears to be a role for C subunit carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at the extreme carboxyl terminus of the C subunit also play an important role in PME-1 binding to a catalytically inactive mutant.
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PMID:A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. 1031 62