Mechanisms of promiscuity among drug metabolizing enzymes and drug transporters.

ABSTRACT: Detoxication, or 'drug-metabolizing', enzymes and drug transporters exhibit remarkable substrate promiscuity and catalytic promiscuity. In contrast to substrate-specific enzymes that participate in defined metabolic pathways, individual detoxication enzymes must cope with substrates of vast structural diversity, including previously unencountered environmental toxins. Presumably, evolution selects for a balance of 'adequate' k_cat /K_M values for a wide range of substrates, rather than optimizing k_cat /K_M for any individual substrate. However, the structural, energetic, and metabolic properties that achieve this balance, and hence optimize detoxication, are not well understood. Two features of detoxication enzymes that are frequently cited as contr

SUBMITTER: Atkins WM 

PROVIDER: S-EPMC7138722 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature