HNF4α is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic β cells.
We have solved the x-ray crystal structure of the HNF4α ligand ...binding domain, which adopts a canonical fold. Two conformational
states are present within each homodimer: an open form with α helix 12 (α12) extended and collinear with α10 and a closed
form with α12 folded against the body of the domain. Although the protein was crystallized without added ligands, the ligand
binding pockets of both closed and open forms contain fatty acids. The carboxylic acid headgroup of the fatty acid ion pairs
with the guanidinium group of Arg 226 at one end of the ligand binding pocket, while the aliphatic chain fills a long, narrow channel that is lined with hydrophobic
residues. These findings suggest that fatty acids are endogenous ligands for HNF4α and establish a framework for understanding
how HNF4α activity is enhanced by ligand binding and diminished by MODY1 mutations.
D-Proline is converted to 5-amino valeric acid by D-proline reductase. This conversion involves the reductive cleavage of the alpha-carbon-nitrogen bond. We have examined the fate of the carboxyl ...oxygen atoms during conversion of D-proline to delta-NH2-valeric acid. 18O atoms from the carboxyl group of D-proline are not lost during conversion to product. In contrast, in the conversion of glycine to acetyl phosphate by glycine reductase a carboxyl oxygen atom is lost to solvent. An intermediate acyl-enzyme is found during the reduction of glycine. We conclude that the reduction of proline proceeds without the formation of an acyl enzyme intermediate.
Epigenetics is the study of the transmission of cell memory through mitosis or meiosis that is not based on the DNA sequence. At the molecular level the epigenetic memory of a cell is embedded in DNA ...methylation, histone post-translational modifications, RNA interference and histone isoform variation. There is a tight link between histone post-translational modifications (the histone code) and DNA methylation, as modifications of histones contribute to the establishment of DNA methylation patterns and vice versa. Interestingly, proteins have recently been identified that can simultaneously read both methylated DNA and the histone code. UHRF1 ful-fills these requirements by having unique structural domains that allow concurrent recognition of histone modifications and methylated DNA. Herein, we review our current knowledge of UHRF1 and discuss how this protein ensures the link between histone marks and DNA methylation. Understanding the molecular functions of this protein may reveal the physiological relevance of the linkage between these layers of epigenetic marks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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