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Time-dependent irreversible inhibition of bovine kidney alkaline phosphatase by oxidized adenosine. Use of this compound as a site-directed inhibitor for studying uncompetitive inhibition.

Authors
Type
Published Article
Journal
Cell biochemistry and function
Publication Date
Volume
12
Issue
4
Pages
263–266
Identifiers
PMID: 7834815
Source
Medline
License
Unknown

Abstract

The L/B/K type of mammalian alkaline phosphatase (ALP) is inhibited uncompetitively by nucleotides. A combination of adenosine and nicotinamide is more effective than either adenosine or nicotinamide alone, probably because a dinucleotide structure is necessary to trigger a conformational change accompanying binding of structures such as NADH. It has been suggested that a loop region containing residue 429 in the ALP polypeptide is important in the interaction of uncompetitive inhibitors with the enzyme. In the L/B/K isoenzyme, residue 429 is a histidine and is a potential target for modification. In an attempt to learn more about the molecular events accompanying inhibition of ALP by uncompetitive inhibitors, bovine kidney ALP was reacted with oxidized adenosine in the presence of nicotinamide to see if site-directed modification occurs. Kidney ALP was irreversibly inactivated by oxidized adenosine but the reaction was slow. The site modified is likely to be close to the region of binding. Sequence data for the kidney enzyme shows that in the region of residue 429 there are no residues except His429 itself that is likely to react with oxidized adenosine.

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