Characterization of human DHRS6, an orphan short chain dehydrogenase/reductase enzyme: a novel, cytosolic type 2 R-beta-hydroxybutyrate dehydrogenase.
|Abstract||Human DHRS6 is a previously uncharacterized member of the short chain dehydrogenases/reductase family and displays significant homologies to bacterial hydroxybutyrate dehydrogenases. Substrate screening reveals sole NAD(+)-dependent conversion of (R)-hydroxybutyrate to acetoacetate with K(m) values of about 10 mm, consistent with plasma levels of circulating ketone bodies in situations of starvation or ketoacidosis. The structure of human DHRS6 w ... [truncated at 450 characters in length]|
|Author||Guo, Kunde; Lukacik, Petra; Papagrigoriou, Evangelos; et al|
|Subject||Amino Acid Motifs Amino Acid Sequence Animals Arginine Binding Sites Cloning, Molecular Crystallography, X-Ray Cytosol Dose-Response Relationship, Drug Exons Green Fluorescent Proteins Hela Cells Humans Hydrogen-Ion Concentration Hydroxybutyrate Dehydrogenase Kinetics Lipids Mitochondria Models, Molecular Molecular Sequence Data Oxidoreductases Phylogeny Protein Conformation Protein Folding Protein Structure, Tertiary Sequence Homology, Amino Acid Substrate Specificity Sulfates chemistry enzymology metabolism metabolism chemistry genetics chemistry metabolism chemistry chemistry|
Structural basis for different specificities of acyltransferases associated with the human cytosolic and mitochondrial fatty acid synthases.
|Abstract||Animals employ two systems for the de novo biosynthesis of fatty acids: a megasynthase complex in the cytosol (type I) that produces mainly palmitate, and an ensemble of freestanding enzymes in the mitochondria (type II) that produces mainly octanoyl moieties. The acyltransferases responsible for initiation of fatty acid biosynthesis in the two compartments are distinguished by their different substrate specificities: the type I enzyme transfers ... [truncated at 450 characters in length]|
|Author||Bunkoczi, Gabor; Misquitta, Stephanie; Wu, Xiaoqiu; et al|
|Subject||Acyltransferases Amino Acid Sequence Catalytic Domain Computer Simulation Crystallography, X-Ray Cytosol Fatty Acid Synthetase Complex, Type I Fatty Acid Synthetase Complex, Type II Fatty Acids Humans Mitochondria Molecular Sequence Data Mutagenesis, Site-Directed Mutant Proteins Sequence Alignment Sequence Homology, Amino Acid Substrate Specificity chemistry genetics metabolism enzymology chemistry metabolism chemistry metabolism biosynthesis enzymology metabolism genetics metabolism|
A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is required for mitochondrial integrity and cell survival.
|Abstract||Deficiency of the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase involved in isoleucine metabolism causes an organic aciduria with atypical neurodegenerative course. The disease-causing gene is HSD17B10 and encodes 17beta-hydroxysteroid dehydrogenase type 10 (HSD10), a protein also implicated in the pathogenesis of Alzheimer's disease. Here we show that clinical symptoms in patients are not correlated with residual enzymatic act ... [truncated at 450 characters in length]|
|Author||Rauschenberger, Katharina; Schöler, Katja; Sass, Jörn Oliver; et al|
|Subject||3-Hydroxyacyl CoA Dehydrogenases Animals Apoptosis Cell Survival Cells, Cultured Fibroblasts Gene Deletion Genetic Complementation Test Humans Hydroxysteroid Dehydrogenases Infant Mice Mice, Knockout Mitochondria Models, Molecular Neurons Protein Structure, Tertiary Xenopus deficiency metabolism metabolism ultrastructure deficiency metabolism physiology ultrastructure physiology|
Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.
|Abstract||Vitamin B(12) (cobalamin, Cbl) is essential to the function of two human enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). The conversion of dietary Cbl to its cofactor forms, methyl-Cbl (MeCbl) for MS and adenosyl-Cbl (AdoCbl) for MUT, located in the cytosol and mitochondria, respectively, requires a complex pathway of intracellular processing and trafficking. One of the processing proteins, MMAA (methylmalonic aciduria type ... [truncated at 450 characters in length]|
|Author||Froese, D Sean; Kochan, Grazyna; Muniz, João R C; et al|
|Subject||Child Child, Preschool Cobamides Crystallography, X-Ray Cytosol Guanosine Diphosphate Guanosine Triphosphate Humans Membrane Transport Proteins Metabolism, Inborn Errors Methylmalonyl-CoA Mutase Mitochondria Mitochondrial Proteins Multiprotein Complexes Mutation, Missense Protein Structure, Quaternary chemistry genetics metabolism chemistry metabolism chemistry genetics metabolism chemistry genetics metabolism chemistry genetics metabolism chemistry genetics metabolism chemistry genetics metabolism chemistry genetics metabolism chemistry genetics metabolism|