Steroid substrate-induced epimerase mechanism in the active site of the human 11β-hydroxysteroid dehydrogenase type 1

Cytochrome P4507B1 7[alpha]-hydroxylates dehydroepiandrosterone (DHEA), epiandrosterone (EpiA) and 5[alpha]-androstane-3[beta],17[beta]-diol (Adiol). 11[beta]-Hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1) interconverts 7[alpha]- and 7[beta]- forms. Whether the inter-conversion proceeds through oxido-reductive steps or epimerase activity is investigated. Experiments using ^3^H-labeled 7[beta]-hydroxy-DHEA, 7[beta]-hydroxy-EpiA and 7[beta]-hydroxy-Adiol show the ^3^H-label to accumulate in 7-oxo-DHEA trap but neither in 7-oxo-EpiA nor 7-oxo-Adiol traps. Computed models of 7-oxygenated steroids dock in the active site of 11[beta]-HSD1 either in a flipped or turned form relative to cortisone and cortisol. 7-Oxo-steroid reduction in 7[alpha]- or 7[beta]-hydroxylated derivatives results from either turned or flipped forms. 11[beta]-HSD1 incubation in H~2~^18^O medium with each 7-hydroxysteroid did not incorporate ^18^O in 7-hydroxylated derivatives of EpiA and Adiol independently of the cofactor used. Thus oxido-reductive steps apply for the interconversion of 7[alpha]- and 7[beta]-hydroxy-DHEA through 7-oxo-DHEA. Epimerisation may proceed on the 7-hydroxylated derivatives of EpiA and Adiol through a mechanism involving the cofactor and Ser170

DFT exchange: sharing perspectives on the workhorse of quantum chemistry and materials science

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 302 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 777 entries, the paper represents a broad snapshot of DFT, anno 2022

20 years of the MS-Xα method

A short overview of the differents steps in the development of the MS-Xα method is given. The main features are underlined, and the applications domains for which this method remains a powerful tool are given and illustrated with selected example

Di-cyclo nonatetraenyl Europium (II) [(η9-C9H9)2]Eu Complexes: Structural Properties, Electronic Structure and Photoluminescence

International audienc

La théorie de la fonctionnelle de la densité : un outil pour l'étude théorique de complexes de coordination

An overview of the possibilities brought by the density functional theory to the coordination chemistry is given. The new trends in the development of the theory are outlined

Structural and electronic analysis of lanthanide complexes : the nature of the lanthanide atom may be not necessarily innocent towards reactivity – a DFT study

Density functional theory (DFT) calculations were used to study a given complex for the whole series of lanthanide cations: [Ln(C3H5)Cp(OMe)] (1) [Ln = La (Z = 57) - Lu (Z = 71)], the radioactive lanthanide promethium (Z = 61) excepted. Contrarily to the common assumptions, the calculations suggest a significant, albeit indirect, contribution of f electrons to bonding. Relativistic effects were considered in the calculations of the bonding energies, as well as in geometry optimisations in both spin-restricted and unrestricted formalisms. The unrestricted orbitals have finally been used for the analysis of the charges and the composition of the frontier orbitals. It is confirmed that the ionic character is more pronounced for complexes of the late lanthanides

Etude théorique des propriétés d'absorption à deux photons des oligomères et dentrimères du 9,9-dihexylfluorène

LYON-ENS Sciences (693872304) / SudocSudocFranceF

Quantitative derivation of the bijective link between molecular data and UV–visible absorption spectra for diluted molecules: guidelines for non specialists

International audienc

Two-photon absorption strength: A new tool for the quantification of two-photon absorption

International audienc