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|
Targeting a uniquely nonspecific prenyl synthase with bisphosphonates to combat cryptosporidiosis.
|Abstract||Cryptosporidiosis is a neglected disease without a wholly effective drug. We present a study demonstrating nitrogen-containing bisphosphonates (N-BPs) to be capable of inhibiting Cryptosporidium parvum at low micromolar concentrations in infected MDCK cells. Predictably, the mechanism of action is based on inhibition of biosynthesis of isoprenoids but the target enzyme is unexpectedly a distinctive C. parvum enzyme dubbed nonspecific polyprenyl p ... [truncated at 450 characters in length]|
|Author||Artz, Jennifer D; Dunford, James E; Arrowood, Michael J; et al|
|Subject||Animals Anti-Infective Agents Cattle Cells, Cultured Chromatography, Liquid Cryptosporidiosis Cryptosporidium parvum Crystallography, X-Ray Dimethylallyltranstransferase Diphosphonates Fluorescent Antibody Technique Humans Inhibitory Concentration 50 Models, Molecular Molecular Structure Protein Prenylation therapeutic use drug therapy drug effects enzymology antagonists and inhibitors metabolism pharmacology therapeutic use|
Quinone oxidoreductase-2-mediated prodrug cancer therapy.
|Abstract||DNA-damaging agents are widely used in cancer treatment despite their lack of tumor specificity. Human NQO2 (quinone oxidoreductase-2) is an atypical oxidoreductase because no endogenous electron donor has been identified to date. The enzyme converts CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide], in the presence of the synthetic nicotinamide cofactor analog EP0152R, to a cytotoxic bifunctional alkylating agent. NQO2 activity in hepatocellular t ... [truncated at 450 characters in length]|
|Author||Middleton, Mark R; Knox, Richard; Cattell, Emma; et al|
|Subject||Adult Aged Antineoplastic Agents Aziridines Cell Death Cross-Linking Reagents Crystallography, X-Ray DNA, Neoplasm Enzyme Activation Female Humans Male Middle Aged Models, Molecular Neoplasms Prodrugs Quinone Reductases adverse effects chemistry pharmacokinetics therapeutic use adverse effects chemistry pharmacokinetics therapeutic use drug effects pharmacology metabolism drug effects drug therapy chemistry pharmacology therapeutic use chemistry metabolism|
Thermolability of mutant MMACHC protein in the vitamin B12-responsive cblC disorder.
|Abstract||Methylmalonic aciduria and homocystinuria, cblC type, is the most common inborn error of cellular vitamin B12 metabolism. We previously showed that the protein carrying the mutation responsible for late-onset cblC (MMACHC-R161Q), treatable with high dose OHCbl, is able to bind OHCbl with wild-type affinity, leaving undetermined the disease mechanism involved [Froese et al., Mechanism of responsiveness, Mol. Genet. Metab. (2009).]. To assess wheth ... [truncated at 450 characters in length]|
|Author||Froese, D S; Healy, S; McDonald, M; et al|
|Subject||Age of Onset Amino Acid Metabolism, Inborn Errors Carrier Proteins Cobamides Fluorometry Homocystinuria Hot Temperature Humans Methylmalonic Acid Protein Denaturation Protein Stability Vitamin B 12 drug therapy genetics chemistry genetics chemistry drug therapy genetics urine analogs and derivatives chemistry genetics therapeutic use|
UDP-glucose dehydrogenase: structure and function of a potential drug target.
|Abstract||Biosynthesis of the glycosaminoglycan precursor UDP-α-D-glucuronic acid occurs through a 2-fold oxidation of UDP-α-D-glucose that is catalysed by UGDH (UDP-α-D-glucose 6-dehydrogenase). Structure-function relationships for UGDH and proposals for the enzymatic reaction mechanism are reviewed in the present paper, and structure-based sequence comparison is used for subclassification of UGDH family members. The eukaryotic group of enzymes (UGDH-II) ... [truncated at 450 characters in length]|
|Author||Egger, Sigrid; Chaikuad, Apirat; Kavanagh, Kathryn L; et al|
|Subject||Animals Enzyme Inhibitors Humans Hyaluronic Acid Neoplasms Uridine Diphosphate Glucose Dehydrogenase Uridine Diphosphate Glucuronic Acid therapeutic use metabolism drug therapy metabolism antagonists and inhibitors chemistry genetics metabolism metabolism|