Trypanotliione reductase and lipoamide dehydrogenase as targets for a structure‐based drug design

Autor:	R Schöneck, R L Krauth-Siegel
Rok vydání:	1995
Předmět:	chemistry.chemical_classification Oxidase test biology Chemistry Stereochemistry Glutathione reductase Substrate (chemistry) Flavoprotein Metabolism Biochemistry Protein structure Enzyme Genetics biology.protein Thiol Molecular Biology Biotechnology
Zdroj:	The FASEB Journal. 9:1138-1146
ISSN:	1530-6860 0892-6638
Popis:	Trypanothione reductase (TR) is a flavoenzyme that has been found only in parasitic protozoa of the order Kinetoplastida. The enzyme catalyzes the NADPH-dependent reduction of glutathionylspermidine conjugates and is a key enzyme of the parasite's thiol metabolism. Consequently, TR is an attractive target molecule for a structure-based drug development against Chagas' disease, African sleeping sickness, and other diseases caused by trypanosomes and leishmanias. The three-dimensional structures of TR and of three enzyme substrate complexes have been solved. Several classes of compounds are discussed as guide structures for the design of specific inhibitors. Among them are tricyclic compounds such as acridines and phenothiazines, which competitively inhibit TR but not the related host enzyme glutathione reductase, as well as oxidase activity-inducing quinones and nitrofurans. Lipoamide dehydrogenase (LipDH) is another flavoprotein discussed as a target molecule for an antitrypanosomal therapy. In Trypanosom...
Databáze:	OpenAIRE
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