Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.
|Abstract||Glutamine synthetase (GS) catalyzes the ligation of glutamate and ammonia to form glutamine, with concomitant hydrolysis of ATP. In mammals, the activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine; there are a number of links between changes in GS activity and neurodegenerative disorders, such as Alzheimer's disease. In plants, because of its importance in the assimilation and re-assimilat ... [truncated at 450 characters in length]|
|Author||Krajewski, Wojciech W; Collins, Ruairi; Holmberg-Schiavone, Lovisa; et al|
|Subject||Adenosine Triphosphate Amino Acid Sequence Animals Apoenzymes Binding Sites Catalytic Domain Cloning, Molecular Crystallography, X-Ray Dogs Drug Design Drug Interactions Glutamate-Ammonia Ligase Herbicides Humans Hydrogen Bonding Kinetics Ligands Magnesium Models, Chemical Models, Molecular Molecular Sequence Data Pharmaceutical Preparations Protein Binding Protein Conformation Protein Structure, Tertiary Sequence Homology, Amino Acid Substrate Specificity Temperature metabolism pharmacology chemistry chemistry genetics isolation and purification metabolism chemical synthesis chemistry metabolism pharmacology chemical synthesis chemistry|
Structural basis for substrate specificity in human monomeric carbonyl reductases.
|Abstract||Carbonyl reduction constitutes a phase I reaction for many xenobiotics and is carried out in mammals mainly by members of two protein families, namely aldo-keto reductases and short-chain dehydrogenases/reductases. In addition to their capacity to reduce xenobiotics, several of the enzymes act on endogenous compounds such as steroids or eicosanoids. One of the major carbonyl reducing enzymes found in humans is carbonyl reductase 1 (CBR1) with a v ... [truncated at 450 characters in length]|
|Author||Pilka, Ewa S; Niesen, Frank H; Lee, Wen Hwa; et al|
|Subject||Alcohol Oxidoreductases Antineoplastic Agents Cloning, Molecular Crystallography, X-Ray Ethanolamines Humans Isoquinolines Kinetics Mutagenesis Mutagenesis, Site-Directed Structure-Activity Relationship Substrate Specificity Temperature Xenobiotics chemistry pharmacology methods chemistry chemistry chemistry|