Structure géométrique de l’ADN

Conference (2012)

L’ADN rassemble les informations nécessaires à tout organisme vivant pour survivre et se reproduire. Ce grimoire vient de ses ancêtres et sera transmis à ses descendants sous une forme légèrement remaniée ... [more ▼]

L’ADN rassemble les informations nécessaires à tout organisme vivant pour survivre et se reproduire. Ce grimoire vient de ses ancêtres et sera transmis à ses descendants sous une forme légèrement remaniée. La géométrie intervient à plusieurs stades de ce processus. [less ▲]

La structure géométrique de l’ADN

in Tangente (2011), 42

Structure Guided Development of Potent Reversibly Binding Penicillin Binding Protein Inhibitors

in ACS Medicinal Chemistry letters (2011), 2 (3)

Following from the evaluation of different types of electrophiles, combined modeling and crystallographic analyses are used to generate potent boronic acid based inhibitors of a penicillin binding protein ... [more ▼]

Following from the evaluation of different types of electrophiles, combined modeling and crystallographic analyses are used to generate potent boronic acid based inhibitors of a penicillin binding protein. The results suggest that a structurally informed approach to penicillin binding protein inhibition will be useful for the development of both improved reversibly binding inhibitors, including boronic acids, and acylating inhibitors, such as β-lactams. [less ▲]

Structure modification in osteoarthritis

in European Musculoskeletal Review (2007)

For decades, the traditional pharmacological management of osteoarthritis (OA) has been mainly symptomatic, despite a lack of evidence of its influence on the duration of the disease and its progression ... [more ▼]

For decades, the traditional pharmacological management of osteoarthritis (OA) has been mainly symptomatic, despite a lack of evidence of its influence on the duration of the disease and its progression. However, in recent years several sets of guidelines, recommendations or points to consider have been issued by regulatory authorities or scientific groups regarding requirements for the registration of drugs to be used in the treatment of OA. The ideal outcomes currently include pain and function assessment for symptom-modifying drugs, and joint-space narrowing (JSN) assessed by plain radiography for structure-modifying compounds. Taking advantage of these more precise recommendations, several chemical entities have been carefully investigated for the management of OA. This article provides a summary of the available evidence demonstrating that some compounds can effectively interfere with the structural progression of the disease. Avocado/Soybean Unsaponifiables The unsaponifiable part of avocado (A) and soybean (S) oils (ASU) mixed in a ratio of 1:2 (A1:S2) has been investigated in the treatment of connective tissues, including in OA, for several years. A pilot randomised, double-blind, placebo-controlled trial with follow-up over two years failed to demonstrate a structural effect of ASU in 163 patients with painful hip OA.1 However, in a post hoc analysis a significant difference was detected in the subgroup with a baseline joint-space width (JSW) smaller than 2.45mm: joint space loss was halved in the treated group (-0.43±0.51mm) compared with the placebo group (-0.86±0.62mm; p=0.01). This finding suggests that ASU may have a structure-modifying effect in patients with severe hip OA. Chondroitine Sulphate Chondroitine sulphate (CS) is a major component of the extra-cellular matrix from many connective tissues, including – but not limited to – cartilage, bone, skin, ligaments and tendons. In the articular cartilage, the high content of CS in the aggrecan plays a major role in creating considerable osmotic swelling pressure, which expands the matrix and places the collagen network under tension. In a pilot double-blind study, JSW measurement on digitalised radiographs of the extended knees was used to compare the effects of CS 800mg/day and a placebo in patients with knee OA.2 There were 23 patients in each group. After one year, JSW was unchanged in the treated group but had decreased by 0.4mm in the placebo group (p<0.005). No significant difference was found for JSW at the narrowest site. The small number of patients for whom end-point values were available (12 in the placebo group and 14 in the CS group) limits the relevance of the results. Another study randomised a total of 120 patients with symptomatic knee OA into two groups receiving either 800mg CS or placebo per day for two periods of three months during one year.3 Radiological progression was assessed as a secondary outcome by automatic measurement of medial femoro-tibial JSW on weight-bearing X-rays of both knees. Radiological progression at month 12 showed significantly decreased JSW in the placebo group, with no change in the CS group. [less ▲]

Structure modifying drugs in osteoarthritis

Conference (2002, November)

The structure of a cold-adapted family 8 xylanase at 1.3 angstrom resolution - Structural adaptations to cold and investigation of the active site

in Journal of Biological Chemistry (2003), 278(9), 7531-7539

Enzymes from psychrophilic organisms differ from their mesophilic counterparts in having a lower thermo-stability and a higher specific activity at low and moderate temperatures. The current consensus is ... [more ▼]

Enzymes from psychrophilic organisms differ from their mesophilic counterparts in having a lower thermo-stability and a higher specific activity at low and moderate temperatures. The current consensus is that they have an increased flexibility, enhancing accommodation and transformation of the substrates at low energy costs. Here we describe the structure of the xylanase from the Antarctic bacterium Pseudoalteromonas haloplanktis at 1.3 Angstrom resolution. Xylanases are usually grouped into glycosyl hydrolase families 10 and 11, but this enzyme belongs to family 8. The fold differs from that of other known xylanases and can be described as an (alpha/alpha)(6) barrel. Various parameters that may explain the cold-adapted properties were examined and indicated that the protein has a reduced number of salt bridges and an increased exposure of hydrophobic residues. The crystal structures of a complex with xylobiose and of mutant D144N were obtained at 1.2 and 1.5 A resolution, respectively. Analysis of the various substrate binding sites shows that the +3 and -3 subsites are rearranged as compared to those of a family 8 homolog, while the xylobiose complex suggests the existence of a +4 subsite. A decreased acidity of the substrate binding cleft and an increased flexibility of aromatic residues lining the subsites may enhance the rate at which substrate is bound. [less ▲]

Structure of a Zn2+-containing D-alanyl-D-alanine-cleaving carboxypeptidase at 2.5 A resolution.

in Nature (1982), 299(5882), 469-470

Bacteria possess proteases that are specific for the peptide bonds between D-alanine residues, one of which has a free alpha-carboxyl group. These D-alanyl-D-alanine peptidases catalyse carboxypeptidation ... [more ▼]

Bacteria possess proteases that are specific for the peptide bonds between D-alanine residues, one of which has a free alpha-carboxyl group. These D-alanyl-D-alanine peptidases catalyse carboxypeptidation and transpeptidation reactions involved in bacterial cell wall metabolism1,2, and are inactivated by beta-lactam antibiotics. We have now elucidated the structure, at 2.5 Å resolution, of the penicillin-resistant Zn2+-containing D-alanyl-D-alanine peptidase of Streptomyces albus (Zn2+ G peptidase)3,4. The enzyme is shown to consist of two globular domains, connected by a single link. The N-terminal domain has three alpha-helices, and the C-terminal domain has three alpha-helices and five beta-strands. The Zn2+ ion is ligated by three histidine residues, and located in a cleft in the C-terminal domain. The mechanism of action of the enzyme may be related to that of other carboxypeptidases, which also contain functional Zn2+ ions. [less ▲]

The structure of di- and tetra-saccharides released from cell walls by lysozyme and streptomyces F1 enzyme and the [beta] (1-->4) N-acetylhexosaminidase activity of these enzymes

in Biochimica et Biophysica Acta (1959), 36(2), 552-554

Structure of growth hormone gene sequences and their expression in bacteria and in cultured cells

in Sato, Gordon; Ross, Russel (Eds.) Hormones and cell culture (1979)

Structure of high-temperature fluid selenium

in Physical Review. B : Condensed Matter (1999), 60(4), 2441-24482448

A semiempirical tight-binding energy model is developed for selenium. It includes s and p electrons as well as an empirical description of the dispersion forces that proves necessary at the liquid ... [more ▼]

A semiempirical tight-binding energy model is developed for selenium. It includes s and p electrons as well as an empirical description of the dispersion forces that proves necessary at the liquid densities under study. The band-structure parameters are obtained by fitting abinitio calculations. The simulated liquid structures are in very good agreement with the most recent X-ray scattering and extended X-ray absorption fine-structure experiments in a broad temperature and density range. The Monte Carlo simulations performed show that the complex liquid structures observed result from the breaking and branching of the selenium chains. The total coordination number is shown to result from the balance between one-, two-, and threefold coordinated atoms. The role of these defects is discussed in relationship with the electrical conductivity of the liquid, i.e., the semiconductor-metal and metal-nonmetal transitions observed at high pressures [less ▲]