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|
Inhibitor scaffolds for 2-oxoglutarate-dependent histone lysine demethylases.
|Abstract||The dynamic methylation of histone lysyl residues plays an important role in biology by regulating transcription, maintaining genomic integrity, and by contributing to epigenetic effects. Here we describe a variety of inhibitor scaffolds that inhibit the human 2-oxoglutarate-dependent JMJD2 subfamily of histone demethylases. Combined with structural data, these chemical starting points will be useful to generate small-molecule probes to analyze t ... [truncated at 450 characters in length]|
|Author||Rose, Nathan R; Ng, Stanley S; Mecinović, Jasmin; et al|
|Subject||Crystallography, X-Ray Dose-Response Relationship, Drug Enzyme Inhibitors Humans Ketoglutaric Acids Models, Molecular Molecular Structure Oxidoreductases, N-Demethylating Protein Structure, Tertiary Stereoisomerism Structure-Activity Relationship pharmacology chemical synthesis chemistry pharmacology antagonists and inhibitors metabolism|
Crystal structure of the PHF8 Jumonji domain, an Nepsilon-methyl lysine demethylase.
|Abstract||Crystallographic analysis of the catalytic domain of PHD finger protein 8 (PHF8), an N(epsilon)-methyl lysine histone demethylase associated with mental retardation and cleft lip/palate, reveals a double-stranded beta-helix fold with conserved Fe(II) and cosubstrate binding sites typical of the 2-oxoglutarate dependent oxygenases. The PHF8 active site is highly conserved with those of the FBXL10/11demethylases, which are also selective for the di ... [truncated at 450 characters in length]|
|Author||Yue, Wyatt W; Hozjan, Viktorija; Ge, Wei; et al|
|Subject||Amino Acid Sequence Binding Sites Crystallography, X-Ray Histone Demethylases Humans Iron Jumonji Domain-Containing Histone Demethylases Ketoglutaric Acids Lysine Models, Molecular Molecular Sequence Data Mutation Protein Binding Protein Conformation Protein Structure, Tertiary Sequence Homology, Amino Acid Transcription Factors genetics chemistry metabolism chemistry genetics metabolism chemistry metabolism chemistry metabolism chemistry genetics metabolism|
Crystal structure of the 2-oxoglutarate- and Fe(II)-dependent lysyl hydroxylase JMJD6.
|Abstract||Lysyl and prolyl hydroxylations are well-known post-translational modifications to animal and plant proteins with extracellular roles. More recent work has indicated that the hydroxylation of intracellular animal proteins may be common. JMJD6 catalyses the iron- and 2-oxoglutarate-dependent hydroxylation of lysyl residues in arginine-serine-rich domains of RNA splicing-related proteins. We report crystallographic studies on the catalytic domain o ... [truncated at 450 characters in length]|
|Author||Mantri, Monica; Krojer, Tobias; Bagg, Eleanor A; et al|
|Subject||Amino Acid Sequence Amino Acid Substitution Base Sequence Catalytic Domain Crystallography, X-Ray DNA Primers Humans Iron Jumonji Domain-Containing Histone Demethylases Ketoglutaric Acids Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutant Proteins Nickel Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase Protein Folding Recombinant Proteins Sequence Homology, Amino Acid Static Electricity genetics metabolism chemistry genetics metabolism metabolism chemistry genetics metabolism metabolism chemistry genetics metabolism chemistry genetics metabolism|