Inhibition of protein tyrosine phosphatases by low-molecular-weight S-nitrosothiols and S-nitrosylated human serum albumin.
The homogeneous recombinant mammalian protein tyrosine phosphatase 1B (PTP1B) and Yersinia protein tyrosine phosphatase (PTPase) are inactivated by a series of low-molecular-weight S-nitrosothiols. These compounds exhibited different inhibitory activities in a time- and concentration-dependent manner with second-order rate constants (k(inact)/K(I)) ranging from 37 to 113 M(-1) min(-1) against mammalian PTP1B and from 66 to 613 M(-1) min(-1) against Yersinia PTPase. Furthermore, the inactivation of Yersinia PTPase by S-nitrosylated protein:S-nitroso human serum albumin was investigated. Both single-S-nitrosylated and poly-S-nitrosylated human serum albumin show good inhibitory ability to Yersinia PTPase. The second-order rate constants are 472 and 1188 M(-1) min(-1), respectively. This result indicates a possibility that S-nitrosylated albumin in vivo may function as an inhibitor for a variety of cysteine-dependent enzymes.
Xian
M
M
Department of Chemistry, Wayne State University, Detroit, Michigan, 48202, USA.
Wang
K
K
Chen
X
X
Hou
Y
Y
McGill
A
A
Zhou
B
B
Zhang
Z Y
ZY
Cheng
J P
JP
Wang
P G
PG
D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008623:Mercaptoethanol; D008970:Molecular Weight; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D026403:S-Nitrosothiols; D012709:Serum Albumin / Q000378:metabolism / Q000494:pharmacology; D015007:Yersinia / Q000201:enzymology
D004791:Enzyme Inhibitors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D012709:Serum Albumin; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; D017027:Protein Tyrosine Phosphatases