64 research outputs found
Lunar laser ranging in infrfared at hte Grasse laser station
For many years, lunar laser ranging (LLR) observations using a green
wavelength have suffered an inhomogeneity problem both temporally and
spatially. This paper reports on the implementation of a new infrared detection
at the Grasse LLR station and describes how infrared telemetry improves this
situation. Our first results show that infrared detection permits us to densify
the observations and allows measurements during the new and the full Moon
periods. The link budget improvement leads to homogeneous telemetric
measurements on each lunar retro-reflector. Finally, a surprising result is
obtained on the Lunokhod 2 array which attains the same efficiency as Lunokhod
1 with an infrared laser link, although those two targets exhibit a
differential efficiency of six with a green laser link
Innovative approach for a classic target: fragment screening on trypanothione reductase reveals new opportunities for drug design
Trypanothione reductase (TR) is a key factor in the redox homeostasis of trypanosomatid parasites, critical for survival in the hostile oxidative environment generated by the host to fight infection. TR is considered an attractive target for the development of new trypanocidal agents as it is essential for parasite survival but has no close homolog in humans. However, the high efficiency and turnover of TR challenging targets since only potent inhibitors, with nanomolar IC50, can significantly affect parasite redox state and viability. To aid the design of effective compounds targeting TR, we performed a fragment-based crystal screening at the Diamond Light Source XChem facility using a library optimized for follow-up synthesis steps. The experiment, allowing for testing over 300 compounds, resulted in the identification of 12 new ligands binding five different sites. Interestingly, the screening revealed the existence of an allosteric pocket close to the NADPH binding site, named the "doorstop pocket" since ligands binding at this site interfere with TR activity by hampering the "opening movement" needed to allow cofactor binding. The second remarkable site, known as the Z-site, identified by the screening, is located within the large trypanothione cavity but corresponds to a region not yet exploited for inhibition. The fragments binding to this site are close to each other and have some remarkable features making them ideal for follow-up optimization as a piperazine moiety in three out of five fragments
Detecting rotational disorder in heme proteins: A comparison between resonance Raman spectroscopy, nuclear magnetic resonance, and circular dichroism
In heme proteins, the canonical and reversed conformations result from the rotation of the heme group by 180° about the α,Îłâmeso axis in the protein pocket. The coexistence of the two different heme orientations has been observed both in proteins reconstituted with hemin and in some native proteins. The reversal of the heme orientation can also change certain functional properties of heme proteins. Complementing the results from other experimental techniques, like circular dichroism and nuclear magnetic resonance, resonance Raman spectroscopy provides detailed information on the structure of the reversed heme. This allows one to elucidate the effects of the heme rotation on the vibrational spectra of the peripheral substituents, especially the vinyl groups. Furthermore, the combination of resonance Raman spectroscopy on single crystals and solution samples of heme proteins is proposed to be a sensitive tool to detect heme orientational disorder, even in the absence of structural data
Neuroglobin, clues to function and mechanism
Neuroglobin is expressed in vertebrate brain and belongs to a branch of the globin family that diverged early in evolution. Sequence conservation and presence in nervous cells of several taxa suggests a relevant role in the nervous system, with tight structural restraints. Twenty years after its discovery, a rich scientific literature provides convincing evidence of the involvement of neuroglobin in sustaining neuron viability in physiological and pathological conditions however, a full and conclusive picture of its specific function, or set of functions is still lacking. The difficulty of unambiguously assigning a precise mechanism and biochemical role to neuroglobin might arise from the participation to one or more cell mechanism that redundantly guarantee the functioning of the highly specialized and metabolically demanding central nervous system of vertebrates. Here we collect findings and hypotheses arising from recent biochemical, biophysical, structural, in cell and in vivo experimental work on neuroglobin, aiming at providing an overview of the most recent literature. Proteins are said to have jobs and hobbies, it is possible that, in the case of neuroglobin, evolution has selected for it more than one job, and support to cover for its occasional failings. Disentangling the mechanisms and roles of neuroglobin is thus a challenging task that might be achieved by considering data from different disciplines and experimental approaches
Self-consistent determination of the Earthâs GM, geocenter motion and figure axis orientation
International audienc
Characterization of an ultra stable quartz oscillator thanks to Time Transfer by Laser Link (T2L2, Jason-2)
International audienc
Temperature, radiation and aging analysis of the DORIS Ultra Stable Oscillator by means of the Time Transfer by Laser Link experiment on Jason-2
International audienc
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