Are protein-tyrosine phosphatases specific for phosphotyrosine?
Protein-tyrosine phosphatases (PTPases) are believed to exhibit restricted specificity toward phosphotyrosine. I demonstrate here that both the Yersinia PTPase and rat PTP1 can dephosphorylate alkyl phosphates such as flavin mononucleotide, pyridoxal 5'-phosphate, D-glucose 6-phosphate, DL-alpha-glycerophosphate, O-phospho-L-serine, and O-phospho-L-threonine. The kcat values for alkyl phosphates are orders of magnitude slower than those for aryl phosphates such as p-nitrophenyl phosphate and O-phospho-L-tyrosine, reflecting the intrinsic lower chemical reactivity of the alkyl phosphates. In addition, the kcat values for the PTPase-catalyzed hydrolysis of alkyl phosphates are similar to the kcat values for the PTPase-catalyzed 18O exchange reaction between inorganic phosphate and water. I conclude that the rate-limiting step for the hydrolysis of alkyl phosphates has changed to the phosphorylation of the PTPases, i.e. the formation of the phosphoenzyme intermediate. The implications of the results described in this report in terms of studying the PTPase catalytic mechanism and their potential application in developing selective PTPase inactivators are discussed.
Zhang
Z Y
ZY
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
D000818:Animals; D002384:Catalysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010755:Organophosphates / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010759:Phosphorus Isotopes; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity; D013379:Substrate Specificity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014867:Water / Q000378:metabolism; D015007:Yersinia / Q000201:enzymology
D010755:Organophosphates; D010710:Phosphates; D010759:Phosphorus Isotopes; D014867:Water; D019000:Phosphotyrosine; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases