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

CsA and FK506 are powerful suppressors of the immune system, most notably of T cells. They act at a point in activation that lies between receptor ligation and the transcription of early genes. Here, Stuart Schreiber and Gerald Crabtree review recent findings that indicate CsA and FK506 operate as prodrugs: they bind endogenous intracellular receptors, the immunophilins, and the resulting complex targets the protein phosphatase, calcineurin, to exert the immunosuppressive effect.
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PMID:The mechanism of action of cyclosporin A and FK506. 137 12

Type 1 protein phosphatase encoded by the GLC7 gene was purified from Saccharomyces cerevisiae as a 1:1 complex with mammalian inhibitor 2 fused to glutathione S-transferase. The complex was inactive and required treatment with Co2+ and trypsin for maximal activity. The specific activity toward phosphorylase a was about 1.8 units/mg of Glc7p, and IC50's for inhibitor 2, okadaic acid, and microcystin-LR were 7.3, 81, and 0.30 nM, respectively. The complex could be activated by glycogen synthase kinase-3 in the presence of Mg2+ and ATP to 20% of the activity seen with Co2+ and trypsin. Thus, the catalytic properties of the yeast type 1 phosphatase are similar to those of the mammalian protein phosphatase 1. The R73C mutant phosphatase from the glycogen-deficient strain, glc7-1, purified as a 1:1 complex with the inhibitor 2 fusion, had a specific activity toward phosphorylase a of 0.9 unit/mg of Glc7p, and IC50's for inhibitor 2, okadaic acid, and microcystin-LR were 13. 1, 113, and 0.37 nM, respectively. The R73C mutation slightly decreases the specific activity and sensitivity to inhibitors, suggesting that changes in biochemical properties may affect glycogen levels. However, the modest changes are consistent with our previous proposal (E. M. Reimann et al., 1993, Adv. Protein Phosphatases 7,173-182) and with the results of Stuart et al. (1994, Mol. Cell. Biol. 14, 896-905) that the mutation may selectively alter the interaction of Glc7p with regulatory proteins.
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PMID:Purification and characterization of type 1 protein phosphatase from Saccharomyces cerevisiae: effect of the R73C mutation. 972 Nov 83

Stuart L. Schreiber is Morris Loeb Professor and Chair of the Department of Chemistry and Chemical Biology at Harvard University, and an Investigator at the Howard Hughes Medical Institute. He founded Harvard's ICCB and directs the NIH-funded Initiative for Chemical Genetics (ICG). He is also a faculty member of the Broad Institute, a joint initiative by Harvard University and MIT that is 'dedicated to leveraging different disciplines to create a new toolkit for genomic medicine'. Following doctoral studies at Harvard University in the laboratory of R. B. Woodward and Y. Kishi, he joined the faculty at Yale University in 1981, where he was promoted to Full Professor in 1986. In 1988, he returned to Harvard, where, in addition to his main roles described above, he is an affiliate of both the Harvard Department of Molecular and Cellular Biology and Harvard Medical School Department of Cell Biology. He is also a member of the Graduate Programs in Biophysics at Harvard University and in Immunology at the Harvard Medical School. In keeping with his multiple roles at Harvard, Schreiber is renowned for taking an integrative and systematic approach to exploring biology. His pioneering work in the field of chemical biology has resulted in the characterisation of many cellular pathways, including (in collaboration with researchers at Stanford University) the identification of the calcium-calcineurin-NFAT signalling pathway. His lab has developed several methodologies including diversity-oriented synthesis (DOS) and in 2003 launched the Chembank public database (), a suite of informatic tools and databases to promote the use of chemical genetics. Schreiber has received many awards and honours including the Tetrahedron Prize for Creativity in Organic Chemistry (1997) and most recently the Society for Biomolecular Screening Achievement Award (2004). He has founded several successful biotechnology firms, including Vertex Pharmaceuticals in 1989, ARIAD Pharmaceuticals in 1991, and Infinity Pharmaceuticals in 2001. He was also founding editor of the journal Chemistry & Biology, which is now in its tenth year of publication.
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PMID:Stuart Schreiber: biology from a chemist's perspective. Interview by Joanna Owens. 1503 26