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Sulfonamide-derivatized galactosides selectively target an unexplored binding site in the galectin-9N-terminal domain

Four directional and positional variants of sulfonamide-derivatized galactopyranosides were synthesized and evaluated against human galectin-1, -3, -4C (C-terminal), -7, -8N (N-terminal), -8C (C-terminal), -9N (N-terminal), and -9C (C-terminal), which revealed that one of the sulfonamide positions and directionalities (methyl 3-{4-[2-(phenylsulfonylamino)-phenyl]-triazolyl}-3-deoxy-α-D-galactopyra

Modeling the Role of a Flexible Loop and Active Site Side Chains in Hydride Transfer Catalyzed by Glycerol-3-phosphate Dehydrogenase

Glycerol-3-phosphate dehydrogenase is a biomedically important enzyme that plays a crucial role in lipid biosynthesis. It is activated by a ligand-gated conformational change that is necessary for the enzyme to reach a catalytically competent conformation capable of efficient transition-state stabilization. While the human form (hlGPDH) has been the subject of extensive structural and biochemical

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with ph

GTP Hydrolysis Without an Active Site Base : A Unifying Mechanism for Ras and Related GTPases

GTP hydrolysis is a biologically crucial reaction, being involved in regulating almost all cellular processes. As a result, the enzymes that catalyze this reaction are among the most important drug targets. Despite their vital importance and decades of substantial research effort, the fundamental mechanism of enzyme-catalyzed GTP hydrolysis by GTPases remains highly controversial. Specifically, ho

Investigating the differences in calculating global mean surface CO2 abundance: the impact of analysis methodologies and site selection

The World Meteorological Organization (WMO) Global Atmosphere Watch (GAW) coordinates high-quality atmospheric greenhouse gas observations globally and provides these observations through the WMO World Data Centre for Greenhouse Gases (WDCGG) supported by Japan Meteorological Agency. The WDCGG and the National Oceanic and Atmospheric Administration (NOAA) analyse these measurements using different

Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1

Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, co

Individual consistency of long-distance migration in a songbird: significant repeatability of autumn route, stopovers and wintering sites but not in timing of migration

Through new tracking techniques, data on timing and routes of migration in long-distance migrant birds are accumulating. However, studies of the consistency of migration of the same individuals between years are still rare in small-sized passerine birds. This type of information is important to understand decisions and migration abilities at the individual level, but also for life history theory,

The dark matter of the cancer genome : Aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations

Cancer is a disease of the genome caused by oncogene activation and tumor suppressor gene inhibition. Deep sequencing studies including large consortia such as TCGA and ICGC identified numerous tumor-specific mutations not only in protein-coding sequences but also in non-coding sequences. Although 98% of the genome is not translated into proteins, most studies have neglected the information hidden

Position of Deltaproteobacteria Cas12e nuclease cleavage sites depends on spacer length of guide RNA

Cas12e proteins (formerly CasX) form a distinct subtype of Class II type V CRISPR-Cas effectors. Recently, it was shown that DpbCas12e from Deltaproteobacteria and PlmCas12e from Planctomycetes can introduce programmable double-stranded breaks in mammalian genomes. Thus, along with Cas9 and Cas12a Class II effectors, Cas12e could be harnessed for genome editing and engineering. The location of cle

Identification of Covalent Binding Sites of Phthalic Anhydride in Human Hemoglobin.

Phthalic anhydride (PA) is a reactive low molecular weight compound used in the chemical industry. The exposure of PA may lead to work-related airway diseases such as rhinitis, chronic bronchitis, and asthma. The exposure gives rise to an increase in hapten-specific IgG antibodies in workers but with a low presence of specific IgE antibodies. In this study, the binding of PA to human hemoglobin (H

An Architecture for Integrated Test Data Compression and Abort-on-Fail Testing in a Multi-Site Environment

The semiconductor technology development makes it possible to fabricate increasingly advanced integrated circuits (ICs). However, because of imperfections at manufacturing, each individual IC must be tested. A major problem at IC manufacturing test is the increasing test data volume as it leads to high automatic test equipment (ATE) memory requirement, long test application time and low throughput

Pharmacophore Refinement and Lead Optimization - A study of the benzodiazepine site of the GABAA receptors

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Wildfire and post-fire management reshape soil microbial guilds and carbon dynamics at a boreal forest site in Sweden

Wildfires are a natural disturbance shaping boreal forests, but their effects on soil microbial communities and biogeochemical cycling remain unclear, particularly in Fennoscandia. We investigated the impact of fire severity and post-fire management on the soil microbial community two years after a boreal wildfire in Sweden. We quantified growth rates of bacteria, saprotrophic fungi (SF), ectomyco

Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family

Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. Case pre