Structure and function of Bs164 {beta}-mannosidase from Bacteroides salyersiae the founding member of glycoside hydrolase family GH164 Protein Structure and Folding

Recent work exploring protein sequence space has revealed a new glycoside hydrolase (GH) family (GH164) of putative mannosidases. GH164 genes are present in several commensal bacteria, implicating these genes in the degradation of dietary glycans. However, little is known about the structure, mechanism of action, and substrate specificity of these enzymes. Herein we report the biochemical characterization and crystal structures of the founding member of this family (Bs164) from the human gut symbiont Bacteroides salyersiae. Previous reports of this enzyme indicated that it has α-mannosidase activity, however, we conclusively show that it cleaves only β-mannose linkages. Using NMR spectroscopy, detailed enzyme kinetics of WT and mutant Bs164, and multiangle light scattering we found that it is a trimeric retaining β-mannosidase, that is susceptible to several known mannosidase inhibitors. X-ray crystallography revealed the structure of Bs164, the first known structure of a GH164, at 1.91 Å resolution. Bs164 is composed of three domains: a (β/α)8 barrel, a trimerization domain, and a β-sandwich domain, representing a previously unobserved structural-fold for β-mannosidases. Structures of Bs164 at 1.80–2.55 Å resolution in complex with the inhibitors noeuromycin, mannoimidazole, or 2,4-dinitrophenol 2-deoxy-2-fluoro-mannoside reveal the residues essential for specificity and catalysis including the catalytic nucleophile (Glu...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Enzymology Source Type: research

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Contributors : Mathieu Boulard ; John R Edwards ; Timothy H BestorSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusMethylated mammalian promoters are transcriptionally silenced even in the presence of all the factors required for their expression. Repression requires the assembly of a methylation-dependent silencing complex that contains the TRIM28 (also known as KAP1 and TIF1 β) protein. An internally controlled interaction screen identified O-linked β-N-acetylglucosamine transferase (O-GlcNAc transferase or ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Source: Infection and Drug Resistance - Category: Infectious Diseases Tags: Infection and Drug Resistance Source Type: research
Polycystic ovary syndrome (PCOS) represents a common endocrine—metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague–Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-f...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Nature Reviews Cardiology, Published online: 21 May 2020; doi:10.1038/s41569-020-0396-6Individuals with obesity have an increased prevalence of the Bacteroides 2 enterotype, which is associated with systemic inflammation and disease. However, statin therapy is associated with a reduced prevalence of this dysbiosis in individuals with obesity.
Source: Nature Reviews Cardiology - Category: Cardiology Authors: Source Type: research
Abstract Bile acids (BA) have emerged as signaling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, e.g. lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 days of age and allocated into control (CON, n=14) or probiotic (PRO, n=14) group fed 50 mg of Lactobacillusplantarum daily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing dama...
Source: The British Journal of Nutrition - Category: Nutrition Authors: Tags: Br J Nutr Source Type: research
This study aimed to assess the effect of interventions by the AS team (AST) on clinical and microbiological outcomes and antimicrobial use. An AS program was introduced at Osaka City University Hospital in January 2014; an interdisciplinary AST was established. We enrolled patients with anaerobic bacteremia between January 2009 and December 2018. Patients were classified into the pre-intervention group (from January 2009 to December 2013) and the post-intervention group (from January 2014 to December 2018). A significant decrease in definitive carbapenem use (P = 0.0242) and an increase in empiric tazobactam/piperacill...
Source: Anaerobe - Category: Microbiology Authors: Tags: Anaerobe Source Type: research
Pyoderma gangrenosum (PG) is a rare, ulcerating, inflammatory disease that is often misdiagnosed as a skin and soft tissue infection. If PG is identified, it is treated with topical or systemic immunosuppressants to reduce inflammation and induce remission. However, the use of immunosuppressants has been linked to a higher risk of superimposed infections. The authors report the case of a 24-year-old female patient with bilateral lower extremity PG with a superimposed infection of Pseudomonas aeruginosa and Bacteroides fragilis after intralesional corticosteroid therapy.
Source: Advances in Skin and Wound Care - Category: Dermatology Tags: ONLINE EXCLUSIVES Source Type: research
Abstract When administrated orally, the vasodilating drug diltiazem can be metabolized into diacetyl diltiazem in the presence of Bacteroides thetaiotaomicron, a human gut microbe. The removal of acetyl group from the parent drug is carried out by the GDSL/SGNH-family hydrolase BT4096. Here the crystal structure of the enzyme was solved by mercury soaking and single-wavelength anomalous diffraction. The protein folds into two parts. The N-terminal part comprises the catalytic domain which is similar to other GDSL/SGNH hydrolases. The flanking C-terminal part is made up of a β-barrel subdomain and an α-h...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
CONCLUSIONS These results indicated that QWBZP improved the diarrhea syndrome with restoring the diversity and adjusting the structures of bacteria in mice intestine, which might reveal the therapeutic mechanism of QWBZP on treating AAD. PMID: 32398636 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Abstract Unique morphologies can enable bacteria to survive in their native environment. Furthermore, many bacteria change their cell shape to adapt to different environmental conditions. For instance, some bacteria increase their surface area under carbon or nitrogen starvation. Bacteriodes thetaiotaomicron is an abundant human gut species; it efficiently degrades a number of carbohydrates and also supports the growth of other bacteria by breaking down complex polysaccharides. The gut provides a variable environment as nutrient availability is subject to the diet and health of the host, yet how gut bacteria adapt...
Source: Microbiology - Category: Microbiology Authors: Tags: Microbiology Source Type: research
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