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Photoaffinity labeling of the 45-kDa and 55-kDa forms of phosphatidylinositol 4-kinase from the yeast Saccharomyces cerevisiae
Journal article   Open access   Peer reviewed

Photoaffinity labeling of the 45-kDa and 55-kDa forms of phosphatidylinositol 4-kinase from the yeast Saccharomyces cerevisiae

G M Carman and Joseph T Nickels
The Journal of biological chemistry, v 268(32), pp 24083-24088
15 Nov 1993
PMID: 8226954
url
https://doi.org/10.1016/S0021-9258(20)80496-7View
Published, Version of Record (VoR) Open

Abstract

1-Phosphatidylinositol 4-Kinase Adenosine Diphosphate - metabolism Adenosine Triphosphate - analogs & derivatives Adenosine Triphosphate - metabolism Adenosine Triphosphate - pharmacology Affinity Labels Azides - pharmacology Kinetics Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) - metabolism Saccharomyces cerevisiae - enzymology Saccharomyces cerevisiae Proteins Substrate Specificity Photochemistry
The membrane-associated 45- and 55-kDa forms of phosphatidylinositol (PI) 4-kinase (ATP:phosphatidylinositol 4-phosphotransferase, EC 2.7.1.67) from Saccharomyces cerevisiae are inhibited by ADP by a competitive mechanism with respect to ATP. We initiated studies toward defining the ATP and ADP sites on the PI 4-kinases using azidonucleotide photoaffinity labeling probes. The photoprobe 8-azido-ATP fulfilled the criteria of a specific photoaffinity label for the 45- and 55-kDa PI 4-kinases. 8-Azido-ATP was a substrate and a competitive inhibitor of the PI 4-kinases with Ki values similar to the Km for ATP. 8-Azido-ATP photoinactivated the enzymes and was photoincorporated into the enzymes in a dose-dependent manner at concentrations similar to the Ki values for the photoprobe. ATP, the true substrate, provided specific protection against photoinactivation and photoincorporation of the PI 4-kinases with 8-azido-ATP, whereas GTP, a nonspecific nucleotide, provided no protection against photoinactivation and photoincorporation. Photoaffinity labeling of the PI 4-kinases with 8-azido-ATP was specifically prevented with ADP. The photoprobe 8-azido-ADP also fulfilled the criteria needed to validate its use as a specific photoprobe for the PI 4-kinases. Photoinactivation of the PI 4-kinases with 8-azido-ADP was prevented specifically with ATP. Taken together, these data supported the conclusion that the ATP and ADP sites on the membrane-associated 45- and 55-kDa PI 4-kinases from S. cerevisiae were the same.

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Biochemistry & Molecular Biology
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