The reaction mechanism of phenylethanolamine N-methyltransferase: A density functional theory study

Hybrid density functional theory methods were used to investigate the reaction mechanism of human phenylethanolamine N-methyltransferase (hPNMT). This enzyme catalyzes the S-adenosyl-l-methionine-dependent conversion of norepinephrine to epinephrine, which constitutes the terminal step in the catecholamine biosynthesis. Several models of the active site were constructed based on the X-ray structure. Geometries of the stationary points along the reaction path were optimized and the reaction barrier and energy were calculated and compared to the experimental values. The calculations demonstrate that the reaction takes place via an S_N2 mechanism with methyl transfer being rate-limiting, a suggestion supported by mutagenesis studies. Optimal agreement with experimental data is reached using a model in which both active site glutamates are protonated. Overall, the mechanism of hPNMT is more similar to those of catechol O-methyltransferase and glycine N-methyltransferase than to that of guanidinoacetate N-methyltransferase in which methyl transfer is coupled to proton transfer.     

Diversity of MLE Helicase Functions in the Regulation of Gene Expression in Higher Eukaryotes

Molecular Biology - The Drosophila melanogaster Maleless (MLE) protein is a conserved helicase involved in a wide range of gene expression regulation processes. A MLE ortholog, named DHX9, was...     

Karyotype,sex determination and male meiosis in three benthic water bugs (Hemiptera: Nepomorpha: Aphelocheiridae)

We report here the first chromosome numbers for benthic water bugs (Nepomorpha: Aphelocheiridae). All three studied species, Aphelocheirus aestivalis (Fabricius, 1794), A. murcius Nieser and Millán, 1989 and Aphelocheirus sp. from Ebro River (northern Spain), have karyotype 2n = 22 + XX/X(0) and inverted sequence of the X chromosome divisions in male meiosis. The similarity and difference in cytogenetic traits between Aphelocheiridae and other families of Nepomorpha are shortly discussed.     

POU2F1 (Oct-1) Differently Autoregulates the Alternative Promoters of Its Own Gene by Binding to Different Regulatory Sites

Molecular Biology - The POU2F1 gene, which plays an important role in regulating the mammalian genome and development, has both a ubiquitous (U) and a tissue-specific (L) promoter and is subject to...