Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chemical modification of
calcineurin
by phenylglyoxal was used to probe for the presence of arginine at, or in close proximity to, the catalytic site of this phosphatase.
Phenylglyoxal
inactivated
calcineurin
with a second-order rate constant of 1.5 M-1 min-1 at pH 7.5 and 30 degrees C. The inactivation reaction was extremely sensitive to Ca2+-induced conformational changes on
calcineurin
; removal of this metal ion from the reaction medium increased the rate of inactivation by almost 1 order of magnitude. Furthermore, significant protection of
calcineurin
by ADP was observed only in the presence of Ca2+, which suggests either that distinct sites are modified by phenylglyoxal in the absence and presence of Ca2+ or that the metal ion promotes binding of ADP to
calcineurin
. Inactivation of
calcineurin
by phenyl[2-14C]glyoxal resulted in the incorporation of more than 12 eq of the reagent. However, a kinetic analysis of the order of the inactivation reaction and complete protection of
calcineurin
by p-nitrophenyl phosphate suggest that only one of the modified residues is responsible for the loss of enzymatic activity. Protection of
calcineurin
by ADP was enhanced severalfold by calmodulin, which correlated well with a calmodulin-stimulated decrease in the Ki for this ligand. Protection of
calcineurin
from inactivation by phenylglyoxal was also observed in the presence of various other nucleotides; half-maximal protection by these poor substrates and competitive inhibitors was observed at concentrations near their respective inhibition constants. Thus, the results of this modification study indicate that at least 1 arginine residue is essential for the expression of catalytic activity of the calmodulin-regulated phosphatase.
...
PMID:Chemical modification of the calmodulin-stimulated phosphatase, calcineurin, by phenylglyoxal. 361 Oct 85
