Inactivation of protein tyrosine phosphatases by dietary isothiocyanates.
Isothiocyanates are bioactive dietary phytochemicals that react readily with protein thiol groups. We find that isothiocyanates are time-dependent inactivators of cysteine-dependent protein tyrosine phosphatases (PTPs). Rate constants for the inactivation of PTP1B and SHP-2 by allyl isothiocyanate and sulforaphane range from 2 to 16 M(-1)s(-1). Results in the context of PTP1B are consistent with a mechanism involving covalent, yet reversible, modification of the enzyme's active site cysteine residue.
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
Sarah M
SM
Lewis
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China.
Ya
Y
Li
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
Michael J
MJ
Catalano
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
Adrian R
AR
Laciak
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
Harkewal
H
Singh
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
Derrick R
DR
Seiner
Department of Veterinary Pathobiology and Veterinary Diagnostic Laboratory, University of Missouri, Columbia, MO 65211, United States.
Thomas J
TJ
Reilly
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States; University of Missouri, Department of Biochemistry, 125 Chemistry Building, Columbia, MO 65211, United States.
John J
JJ
Tanner
University of Missouri, Department of Chemistry, 125 Chemistry Building, Columbia, MO 65211, United States; University of Missouri, Department of Biochemistry, 125 Chemistry Building, Columbia, MO 65211, United States. Electronic address: gatesk@missouri.edu.
Kent S
KS
Gates
D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017879:Isothiocyanates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D017879:Isothiocyanates; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
Enzyme inactivation; Isothiocyanate; PTP; Phosphatase; Sulforaphane