title: Ornithine aminotransferase versus GABA aminotransferase: implications for the design of new anticancer drugs.
abstract: Ornithine aminotransferase (OAT) and γ-aminobutyric acid aminotransferase (GABA-AT) are classified under the same evolutionary subgroup and share a large portion of structural, functional, and mechanistic features. Therefore, it is not surprising that many molecules that bind to GABA-AT also bind well to OAT. Unlike GABA-AT, OAT had not been viewed as a potential therapeutic target until recently; consequently, the number of therapeutically viable molecules that target OAT is very limited. In this review the two enzymes are compared with respect to their active-site structures, catalytic and inactivation mechanisms, and selective inhibitors. Insight is offered that could aid in the design and development of new selective inhibitors of OAT for the treatment of cancer.
authors.affiliation: Center for Molecular Innovation and Drug Discovery, Department of Chemistry, Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois.
authors.forename: Hyunbeom
authors.initials: H
authors.lastname: Lee
authors.forename: Jose I
authors.initials: JI
authors.lastname: Juncosa
authors.forename: Richard B
authors.initials: RB
authors.lastname: Silverman
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020134:Catalytic Domain; D015195:Drug Design; D006801:Humans; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009953:Ornithine-Oxo-Acid Transaminase; D000612:4-Aminobutyrate Transaminase
keywords: gamma-aminobutyric acid aminotransferase (GABA-AT); hepatocellular carcinoma (HCC); irreversible enzyme inhibition; ornithine aminotransferase (OAT)