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 activity of two purified homogeneous phosphoprotein phosphatases types P I and P II) (phosphoprotein phosphohydrolase, EC 3.1.3.16) from rabbit liver (Khandelwal, R.L., Vandenheede, J.R., and Krebs, E.G. (1976) J. Biol. Chem. 251, 4850-4858) were examined in the presence of divalent cations, Pi, PPi, nucleotides, glycolytic intermediates and a number of other compounds using phosphorylase a, glycogen synthase D and phosphorylated histone as substrates. Enzyme activities were usually inhibited by divalent cations with all substrates; the inhibition being more pronounced with phosphorylase a. Zn2+ was the most potent inhibitor among the divalent cations tested. The enzyme was competitively inhibited by PPi (Ki = 0.1 mM for P I and 0.3 mM for PII), Pi (Ki = 15 mM for P I and 19.8 mM for P II) and p-nitrophenyl phosphate (Ki = 1 mM and 1.4 mM for P I and P II, respectively) employing phosphorylase a as the substrate. The compounds along with a number of others (Na2SO4, citrate, NaF and EDTA) also inhibited the enzyme activity with the other two substrates. Severe inhibition of the enzyme was also observed in the presence of the adenine and uridine nucleotides; monophosphate nucleotides being more inhibitory with phosphorylase a, whereas the di- and triphosphate nucleotides showed more inhibition with glycogen synthase D and phosphorylated histone. Cyclic AMP had no significant effect on enzyme activity with all the substrates tested. Phosphorylated metabolites did not show any marked effect on the enzyme activity with phosphorylase a as the substrate.
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PMID:Some properties of purified phosphoprotein phosphatases from rabbit liver. 20 Feb 72

Microcystins (MCs) are cyanobacterial toxins that inhibit protein phosphatases 1 and 2A (PP1, PP2A) within an animal through both reversible and covalent interactions. Only MCs that have accumulated in animal tissue in reversible interactions are currently considered when estimating risk to higher trophic levels and humans through food web exposure. However, the majority of MCs is likely covalently bound to target proteins in tissues and these MCs are not quantified or included in these assessments. These covalently bound MCs may be made bioavailable in the digestive system of a consumer through the digestion of their attached protein phosphatase. Three common digestive enzymes, pepsin, chymotrypsin, and trypsin, did not digest cyclic MC-LR and MC-LY, but were very active against a control peptide with typical linkages and standard amino acids in "L" conformation, supporting the possibility for MC-peptide formation during gut passage. To test if digestion products could be biologically active in the consumer, four predicted MC-peptides were synthesized and assayed for activity against PP1 by the protein phosphatase inhibition assay (PPIA). All four MC-peptides were active against PP1 and comparably half (58%) as inhibitory as the parent toxin. This in vitro study demonstrated that MCs covalently bound to proteins may represent a reservoir of potential toxicity for consumers.
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PMID:Possible mechanism for the foodweb transfer of covalently bound microcystins. 2007 Oct 28