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|
Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs.
|Abstract||p21-activated kinases have been classified into two groups based on their domain architecture. Group II PAKs (PAK4-6) regulate a wide variety of cellular functions, and PAK deregulation has been linked to tumor development. Structural comparison of five high-resolution structures comprising all active, monophosphorylated group II catalytic domains revealed a surprising degree of domain plasticity, including a number of catalytically productive an ... [truncated at 450 characters in length]|
|Author||Eswaran, Jeyanthy; Lee, Wen Hwa; Debreczeni, Judit E; et al|
|Subject||Amino Acid Sequence Animals Catalytic Domain Crystallography Molecular Sequence Data Protein Conformation Protein Kinase Inhibitors Protein-Serine-Threonine Kinases Purines drug effects genetics chemistry pharmacology antagonists and inhibitors chemistry genetics chemistry|
Medium- and short-chain dehydrogenase/reductase gene and protein families : the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes.
|Abstract||Short-chain dehydrogenases/reductases (SDRs) constitute a large family of NAD(P)(H)-dependent oxidoreductases, sharing sequence motifs and displaying similar mechanisms. SDR enzymes have critical roles in lipid, amino acid, carbohydrate, cofactor, hormone and xenobiotic metabolism as well as in redox sensor mechanisms. Sequence identities are low, and the most conserved feature is an alpha/beta folding pattern with a central beta sheet flanked by ... [truncated at 450 characters in length]|
|Author||Kavanagh, K L; Jörnvall, H; Persson, B; et al|
|Subject||Alcohol Dehydrogenase Animals Catalytic Domain Humans Multigene Family Oxidoreductases Protein Structure, Secondary chemistry metabolism chemistry genetics metabolism|
Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site.
|Abstract||About 10% of all protein kinases are predicted to be enzymatically inactive pseudokinases, but the structural details of kinase inactivation have remained unclear. We present the first structure of a pseudokinase, VRK3, and that of its closest active relative, VRK2. Profound changes to the active site region underlie the loss of catalytic activity, and VRK3 cannot bind ATP because of residue substitutions in the binding pocket. However, VRK3 stil ... [truncated at 450 characters in length]|
|Author||Scheeff, Eric D; Eswaran, Jeyanthy; Bunkoczi, Gabor; et al|
|Subject||Adenosine Triphosphate Amino Acid Sequence Binding Sites Catalytic Domain Models, Molecular Molecular Sequence Data Phosphotransferases Protein Conformation Protein Folding metabolism chemistry metabolism|
Crystal structure of human carbonic anhydrase-related protein VIII reveals the basis for catalytic silencing.
|Author||Picaud, Sarah S; Muniz, João R C; Kramm, Anneke; et al|
|Subject||Catalysis Catalytic Domain Crystallography, X-Ray Humans Models, Molecular Protein Conformation Tumor Markers, Biological chemistry metabolism|