Mechanism of Inactivation of Glutamine Amidotransferases
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چکیده
L-(aS, 5S)-a-Amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125), an antitumor drug isolated from Streptomyces sviceus, is an active site-directed affinity analog of glutamine, I t selectively inactivates the glutamine-dependent activities of two bacterial glutamine amidotransferases, anthranilate synthase and glutamate synthase. A reversible noncovalent complex is formed prior to irreversible enzyme modification. Inactivation of anthranilate synthase results from incorporation of approximately 1 eq of AT-l25/enzyme protomer. Active site cysteine-83 in Serratia marcescens anthranilate synthase Component I1 is the residue alkylated by AT-125. Anthranilate synthase is rapidly inactivated by AT-125 in S. marcescens cells. In vivo inactivation is by the same mechanism as in vitro.
منابع مشابه
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تاریخ انتشار 2001