The effects of substrates, products and other ligands on the susceptibility of inositol monophosphatase to proteolysis by endoprotease lys-C.
Inositol monophosphatase is cleaved by endoprotease lys-C at a single site (Lys36-Ser37). The rate of proteolysis is greatly reduced in the presence of substrate (D,L-Ins(1)P) and Mg2+, and less so in the presence of Pi and Mg2+, consistent with protection of the susceptible bond in the E-P or E-Pi states of the enzyme. Potentiation by Li+ of the protection afforded by a substrate analogue, 1S-phosphoryloxy-2R,4S-dihydroxycyclohexane, and Mg2+ supports the idea that Li+ binds to the E-P state.
Gee
N S
NS
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Knowles
M R
MR
McAllister
G
G
Ragan
C I
CI
D003511:Cyclohexanols / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008024:Ligands; D008094:Lithium / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008666:Metalloendopeptidases; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D013379:Substrate Specificity
D003511:Cyclohexanols; D007295:Inositol Phosphates; D008024:Ligands; D009943:Organophosphorus Compounds; C069565:1-phosphoryloxy-2,4-dihydroxycyclohexane; D008094:Lithium; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D010450:Endopeptidases; D008666:Metalloendopeptidases; C039830:peptidyl-Lys metalloendopeptidase; D008274:Magnesium