http://hub.hku.hk/bitstream/10722/289788/1/content.pdf

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.

Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.

/pdf/zika-virus-in-the-americas-early-epidemiological-and-genetic-4lm8dhvubw.pdf

Zika virus in the Americas: Early epidemiological and genetic findings

https://doi.org/10.1016/j.cell.2021.12.046

SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer.

The Bcl-2 family of proteins controls a critical step in commitment to apoptosis by regulating permeabilization of the mitochondrial outer membrane (MOM). The family is divided into three classes: multiregion proapoptotic proteins that directly permeabilize the MOM; BH3 proteins that directly or indirectly activate the pore-forming class members; and the antiapoptotic proteins that inhibit this process at several steps. Different experimental approaches have led to several models, each proposed to explain the interactions between Bcl-2 family proteins. The discovery that many of these interactions occur at or in membranes as well as in the cytoplasm, and are governed by the concentrations and relative binding affinities of the proteins, provides a new basis for rationalizing these models. Furthermore, these dynamic interactions cause conformational changes in the Bcl-2 proteins that modulate their apoptotic function, providing additional potential modes of regulation.

/pdf/mechanisms-of-action-of-bcl-2-family-proteins-1rimujikqe.pdf

Mechanisms of Action of Bcl-2 Family Proteins

ENDscript 2 is a friendly Web server for extracting and rendering a comprehensive analysis of primary to quaternary protein structure information in an automated way. This major upgrade has been fully re-engineered to enhance speed, accuracy and usability with interactive 3D visualization. It takes advantage of the new version 3 of ESPript, our well-known sequence alignment renderer, improved to handle a large number of data with reduced computation time. From a single PDB entry or file, ENDscript produces high quality figures displaying multiple sequence alignment of proteins homologous to the query, colored according to residue conservation. Furthermore, the experimental secondary structure elements and a detailed set of relevant biophysical and structural data are depicted. All this information and more are now mapped on interactive 3D PyMOL representations. Thanks to its adaptive and rigorous algorithm, beginner to expert users can modify settings to fine-tune ENDscript to their needs. ENDscript has also been upgraded as an open platform for the visualization of multiple biochemical and structural data coming from external biotool Web servers, with both 2D and 3D representations. ENDscript 2 and ESPript 3 are freely available at http://endscript.ibcp.fr and http://espript.ibcp.fr, respectively.

/pdf/deciphering-key-features-in-protein-structures-with-the-new-3kiylhufbn.pdf

Deciphering key features in protein structures with the new ENDscript server

Trehalulose Synthase Native and Carbohydrate Complexed Structures Provide Insights into Sucrose Isomerization

The implications of Asn315 and Val450 in the atypical starch hydrolysis profile of Bacillus stearothermophilus Amy (a-amylase) US100 have been suggested previously [Ben Ali, Mhiri, Mezghani and Bejar (2001) Enzyme Microb. Tech. 28, 537-542]. In order to confirm this hypothesis, three mutants were generated. Of these two have a single mutation, N315D or V450G, whereas the third contains both mutations. Analysis of the starch breakdown-profile of these three mutants, as well as of the wild-type, allowed us to conclude that each single mutation induces a small variation in the hydrolysis product. However, the major end product produced by the double mutant shifts from maltopentaose/maltohexaose to maltose/maltotriose, confirming the involvement of these two residues in starch hydrolysis. The superimposition of AmyUS100 model with that of Bacillus licheniformis shows in AmyUS100 an additional loop containing residues Ile214 and Gly215. Remarkably, the deletion of these two residues increases the half-life at 100 degrees C from 15 min to approx. 70 min. Moreover, this engineered amylase requires less calcium, 25 p.p.m. instead of 100 p.p.m., to reach maximal thermostability.

/pdf/thermostability-enhancement-and-change-in-starch-hydrolysis-4s026gpkno.pdf

Thermostability enhancement and change in starch hydrolysis profile of the maltohexaose-forming amylase of Bacillus stearothermophilus US100 strain.

The invention concerns the use of a polyamine derivative or a polyamine for inhibiting the active site of glycosidase enzymes intervening in the transformation of polysaccharides into sugars, in particular into glucose, in a living organism and the use of a polyamine derivative for preparing a medicine for diagnosing, preventing or treating pathologies involving metabolic disorders related to glycosidases, and more particularly a dysfunction of intestinal absorption of glucose, such as non-insulin-dependent diabetes, obesity, hyperglycaemia, or hyperlipidemia.

Xavier Robert

Papers

Deciphering key features in protein structures with the new ENDscript server

Trehalulose Synthase Native and Carbohydrate Complexed Structures Provide Insights into Sucrose Isomerization

Thermostability enhancement and change in starch hydrolysis profile of the maltohexaose-forming amylase of Bacillus stearothermophilus US100 strain.

Novel glycosidase inhibitors and their pharmacological uses, in particular for treating diabetes

The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus