Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease.
|Abstract||Refsum disease (RD), a neurological syndrome characterized by adult onset retinitis pigmentosa, anosmia, sensory neuropathy, and phytanic acidaemia, is caused by elevated levels of phytanic acid. Many cases of RD are associated with mutations in phytanoyl-CoA 2-hydroxylase (PAHX), an Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes the initial alpha-oxidation step in the degradation of phytenic acid in peroxisomes. We describe t ... [truncated at 450 characters in length]|
|Author||McDonough, Michael A; Kavanagh, Kathryn L; Butler, Danica; et al|
|Subject||Aspartic Acid Binding Sites Coenzyme A Crystallization Crystallography, X-Ray Cysteine Escherichia coli Ferrous Compounds Histidine Humans Ketoglutaric Acids Mixed Function Oxygenases Models, Molecular Mutation Peroxisomes Phytanic Acid Protein Binding Protein Structure, Secondary Recombinant Proteins Refsum Disease Structure-Activity Relationship Transfection metabolism genetics metabolism metabolism genetics metabolism metabolism metabolism chemistry genetics enzymology analogs and derivatives metabolism drug therapy enzymology|
Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology.
|Abstract||Carbonyl groups are frequently found in endogenous or xenobiotic compounds. Reactive carbonyls, formed during lipid peroxidation or food processing, and xenobiotic quinones are able to covalently modify DNA or amino acids. They can also promote oxidative stress, the products of which are thought to be an important initiating factor in degenerative diseases or cancer. Carbonyl groups are reduced by an array of distinct NADPH-dependent enzymes, bel ... [truncated at 450 characters in length]|
|Subject||Alcohol Oxidoreductases Animals Humans Mammals NADH, NADPH Oxidoreductases Oxidative Stress Quinones Structure-Activity Relationship Xenobiotics metabolism physiology metabolism metabolism|
Potassium channel structures: do they conform?
|Abstract||Potassium channels are signalling elements vital to vertebrate neurotransmission, and cardiac and renal function. Two inherent qualities equip them for their role in the interconversion of chemical and electrical messages: high selectivity for potassium ions and the ability to open (gate) on cue. The crystal structure of KcsA, published in 1998, explained much about potassium selectivity and high ion flux. The enormous diversity of potassium chan ... [truncated at 450 characters in length]|
|Author||Gulbis, Jacqueline M; Doyle, Declan A;|
|Subject||Ion Channel Gating Ion Transport Ligands Models, Molecular Potassium Potassium Channels Protein Conformation Signal Transduction Structure-Activity Relationship physiology metabolism chemistry metabolism physiology|
Structural analysis identifies imidazo[1,2-b]pyridazines as PIM kinase inhibitors with in vitro antileukemic activity.
|Abstract||Much attention has recently been focused on PIM kinases as potential targets for the treatment of hematopoietic malignancies and some solid cancers. Using protein stability shift assays, we identified a family of imidazo[1,2-b]pyridazines to specifically interact with and inhibit PIM kinases with low nanomolar potency. The high-resolution crystal structure of a PIM1 inhibitor complex revealed that imidazo[1,2-b]pyridazines surprisingly interact w ... [truncated at 450 characters in length]|
|Author||Pogacic, Vanda; Bullock, Alex N; Fedorov, Oleg; et al|
|Subject||Animals Antineoplastic Agents Cell Line, Tumor Chemistry, Pharmaceutical Drug Design Enzyme Inhibitors Humans Inhibitory Concentration 50 Mice Models, Chemical Models, Molecular Protein Binding Protein-Serine-Threonine Kinases Proto-Oncogene Proteins Proto-Oncogene Proteins c-pim-1 Pyridazines Structure-Activity Relationship pharmacology methods chemistry pharmacology antagonists and inhibitors antagonists and inhibitors chemistry|
Structural and functional characterization of the human protein kinase ASK1.
|Abstract||Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases. Here, we present the structure of the human ASK1 catalytic domain in complex with staurosporine. Analytical ultracentrifugation (AUC) and crystallographic analysis showed that ASK1 forms a tight dimer (K(d) approximately 0.2 microM) interacting in a head-to-tail fashion. We found that the AS ... [truncated at 450 characters in length]|
|Author||Bunkoczi, Gabor; Salah, Eidarus; Filippakopoulos, Panagis; et al|
|Subject||Amino Acid Sequence Binding Sites Catalysis Dimerization Enzyme Activation Enzyme Inhibitors Humans MAP Kinase Kinase Kinase 5 Models, Molecular Molecular Sequence Data Phosphorylation Protein Conformation Protein Structure, Tertiary Staurosporine Structure-Activity Relationship Substrate Specificity chemistry metabolism chemistry metabolism chemistry metabolism|