12 results match your criteria males  = 4086

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Development of Non-Hydrolysable Oligosaccharide Activity-Based Inactivators for Endoglycanases: A Case Study on α-1,6 Mannanases.

Chemistry 2021 Jul 21;27(37):9519-9523. Epub 2021 May 21.

Department of Chemistry, York Structural Biology Laboratory, University of York, Heslington, York, YO10 5DD, UK.

There is a vast genomic resource for enzymes active on carbohydrates. Lagging far behind, however, are functional chemical tools for the rapid characterization of carbohydrate-active enzymes. Activity-based probes (ABPs) offer one chemical solution to these issues with ABPs based upon cyclophellitol epoxide and aziridine covalent and irreversible inhibitors representing a potent and widespread approach. Read More

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Mannosidase mechanism: at the intersection of conformation and catalysis.

Curr Opin Struct Biol 2020 06 28;62:79-92. Epub 2019 Dec 28.

School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address:

Mannosidases are a diverse group of enzymes that are important in the biological processing of mannose-containing polysaccharides and complex glycoconjugates. They are found in 12 of the >160 sequence-based glycosidase families. We discuss evidence that nature has evolved a small set of common mechanisms that unite almost all of these mannosidase families. Read More

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Molecular mechanisms regulating O-linked N-acetylglucosamine (O-GlcNAc)-processing enzymes.

Curr Opin Chem Biol 2019 12 22;53:131-144. Epub 2019 Oct 22.

Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada. Electronic address:

The post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) dynamically programmes cellular physiology to maintain homoeostasis and tailor biochemical pathways to meet context-dependent cellular needs. Despite diverse roles of played by O-GlcNAc, only two enzymes act antagonistically to govern its cycling; O-GlcNAc transferase installs the monosaccharide on target proteins, and O-GlcNAc hydrolase removes it. The recent literature has exposed a network of mechanisms regulating these two enzymes to choreograph global, and target-specific, O-GlcNAc cycling in response to cellular stress and nutrient availability. Read More

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December 2019

A Family of Dual-Activity Glycosyltransferase-Phosphorylases Mediates Mannogen Turnover and Virulence in Leishmania Parasites.

Cell Host Microbe 2019 Sep;26(3):385-399.e9

Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address:

Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of β-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. Read More

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September 2019

Distortion of mannoimidazole supports a B boat transition state for the family GH125 α-1,6-mannosidase from Clostridium perfringens.

Org Biomol Chem 2019 08;17(34):7863-7869

York Structural Biology Laboratory, Department of Chemistry, The University of York, YO10 5DD York, UK.

Enzyme transition-state mimics can act as powerful inhibitors and allow structural studies that report on the conformation of the transition-state. Here, mannoimidazole, a mimic of the transition state of mannosidase catalyzed hydrolysis of mannosides, is shown to bind in a B2,5 conformation on the Clostridium perfringens GH125 α-1,6-mannosidase, providing additional evidence of a OS2-B2,5-1S5 conformational itinerary for enzymes of this family. Read More

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Structural studies of a surface-entropy reduction mutant of O-GlcNAcase.

Acta Crystallogr D Struct Biol 2019 Jan 8;75(Pt 1):70-78. Epub 2019 Jan 8.

Department of Chemistry, University of York, York YO10 5DD, England.

The enzyme O-GlcNAcase catalyses the removal of the O-GlcNAc co/post-translational modification in multicellular eukaryotes. The enzyme has become of acute interest given the intimate role of O-GlcNAcylation in tau modification and stability; small-molecular inhibitors of human O-GlcNAcase are under clinical assessment for the treatment of tauopathies. Given the importance of structure-based and mechanism-based inhibitor design for O-GlcNAcase, it was sought to test whether different crystal forms of the human enzyme could be achieved by surface mutagenesis. Read More

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January 2019

Conformational Analysis of the Mannosidase Inhibitor Kifunensine: A Quantum Mechanical and Structural Approach.

Chembiochem 2017 08 26;18(15):1496-1501. Epub 2017 Jun 26.

York Structural Biology Laboratory, Department of Chemistry, The University of York, York, YO10 5DD, UK.

The varied yet family-specific conformational pathways used by individual glycoside hydrolases (GHs) offer a tantalising prospect for the design of tightly binding and specific enzyme inhibitors. A cardinal example of a GH-family-specific inhibitor, and one that finds widespread practical use, is the natural product kifunensine, which is a low-nanomolar inhibitor that is selective for GH family 47 inverting α-mannosidases. Here we show, through quantum-mechanical approaches, that kifunensine is restrained to a "ring-flipped" C conformation with another accessible, but higher-energy, region around the B conformation. Read More

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Conformational Behaviour of Azasugars Based on Mannuronic Acid.

Chembiochem 2017 07 18;18(13):1297-1304. Epub 2017 Apr 18.

Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.

A set of mannuronic-acid-based iminosugars, consisting of the C-5-carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH-dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an "inverted" C chair conformation as opposed to the "normal" C chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Read More

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Computational Design of Experiment Unveils the Conformational Reaction Coordinate of GH125 α-Mannosidases.

J Am Chem Soc 2017 01 3;139(3):1085-1088. Epub 2017 Jan 3.

Departament de Química Inorgànica i Orgànica (Secció de Química Orgànica) & Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona , 08028 Barcelona, Spain.

Conformational analysis of enzyme-catalyzed mannoside hydrolysis has revealed two predominant conformational itineraries through B or H transition-state (TS) conformations. A prominent unassigned catalytic itinerary is that of exo-1,6-α-mannosidases belonging to CAZy family 125. A published complex of Clostridium perfringens GH125 enzyme with a nonhydrolyzable 1,6-α-thiomannoside substrate mimic bound across the active site revealed an undistorted C conformation and provided no insight into the catalytic pathway of this enzyme. Read More

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January 2017

Crystal structures of penicillin-binding protein 3 in complexes with azlocillin and cefoperazone in both acylated and deacylated forms.

FEBS Lett 2016 Jan 23;590(2):288-97. Epub 2016 Jan 23.

Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Oxford, UK.

Penicillin-binding protein 3 (PBP3) from Pseudomonas aeruginosa is the molecular target of β-lactam-based antibiotics. Structures of PBP3 in complexes with azlocillin and cefoperazone, which are in clinical use for the treatment of pseudomonad infections, have been determined to 2.0 Å resolution. Read More

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January 2016

Elderly patients' preferences concerning life-support treatment.

Anaesthesia 1993 Dec;48(12):1027-33

Department of Anaesthesia, Norfolk and Norwich Hospital.

The preferences of 118 elderly patients, aged from 70 to 97 years, concerning the institution of artificial ventilation in the event of an overwhelming illness, were investigated using a questionnaire. Most patients wanted treatment if the outcome was likely to be good, but in approximately half, the desire for treatment declined as anticipated quality of life or chances of recovery fell. Forty percent wanted to make the decision about institution of artificial ventilation themselves if mentally competent and 24% wanted to use some form of advance directive if mentally incompetent. Read More

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December 1993

Mastoid misery: quantifying the distress in a radical cavity.

Authors:
A G Males R F Gray

Clin Otolaryngol Allied Sci 1991 Feb;16(1):12-4

Department of Otolaryngology, Addenbrooke's Hospital, Cambridge, UK.

Seventy-eight mastoid cavities were studied in 39 patients who required revision surgery for troublesome symptoms. A retrospective questionnaire was used to assign a symptom score to each patient in his pre and post-operative condition. The 5 leading symptoms of pain, wax, discharge, smell and giddiness were reviewed. Read More

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February 1991
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