'Irreversible' slow-onset inhibition of orotate phosphoribosyltransferase by an amidrazone phosphate transition-state
John F Witte1, Kathryn E Bray, Chelsea K Thornburg
1Arthur F. Scott Laboratory of Chemistry, Reed College, Portland, OR 97202-8199, USA.
Bioorganic & Medicinal Chemistry Letters
|September 19, 2006
Abstract:
A mimic of the putative transition-state intermediate has been synthesized and found to be a very slow-onset inhibitor of yeast orotate phosphoribosyltransferase. The mechanism of inhibition may involve a rate-determining isomerization of the enzyme to a form receptive to the inhibitor, which then remains tightly bound.
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