Sökning: "protein redesign"

Visar resultat 1 - 5 av 14 avhandlingar innehållade orden protein redesign.

  1. 1. Mutational Analysis and Redesign of Alpha-class Glutathione Transferases for Enhanced Azathioprine Activity

    Författare :Olof Modén; Bengt Mannervik; Mikael Widersten; Kenneth Tew; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; TEKNIK OCH TEKNOLOGIER; ENGINEERING AND TECHNOLOGY; allelic variants; azathioprine; bioactivation; chimeric mutagenesis; directed evolution; DNA shuffling; enzyme engineering; glutathione transferase; GST; lysate screening; molecular docking; multiple alignment; multivariate analysis; polymorphism; principal component analysis; prodrug; prodrug activation; protein engineering; protein redesign; reduced amino acid alphabet; saturation mutagenesis; semi-rational enzyme engineering; site-directed mutagenesis; structure-activity relationship; structure-based redesign; Biokemi; Biochemistry;

    Sammanfattning : Glutathione transferase (GST) A2-2 is the human enzyme most efficient in catalyzing azathioprine activation. Structure-function relationships were sought explaining the higher catalytic efficiency compared to other alpha class GSTs. LÄS MER

  2. 2. Modulating Enzyme Functions by Semi-Rational Redesign and Chemical Modifications : A Study on Mu-class Glutathione Transferases

    Författare :Malena A Norrgård; Bengt Mannervik; Birgitta Tomkinson; Timothy Mantle; Uppsala universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; protein redesign; semi-rational redesign; saturation mutagenesis; iterative saturation mutagenesis; chemical modification; Cys; Cys-X scanning; enzyme evolution; promiscuous; substrate selectivity; enantioselectivity; Biochemistry; Biokemi; Biokemi; Biochemistry;

    Sammanfattning : Today, enzymes are extensively used for many industrial applications, this includes bulk and fine-chemical synthesis, pharmaceuticals and consumer products. Though Nature has perfected enzymes for many millions of years, they seldom reach industrial performance targets. LÄS MER

  3. 3. Evolutionary Analysis and Posttranslational Chemical Modifications in Protein Redesign : A Study on Mu Class Glutathione Transferases

    Författare :Ylva Ivarsson; Bengt Mannervik; Gun Stenberg; Richard N. Armstrong; Uppsala universitet; []
    Nyckelord :Biochemistry; glutathione transferase; evolutionary analysis; positive selection; epoxide; stereoselectivity; protein modification; Biokemi;

    Sammanfattning : Glutathione transferases (GSTs) constitute a family of multifarious enzymes that conjugate glutathione (GSH) with a wide range of electrophiles. GSTs are grouped into different classes based on protein sequence similarities. Despite high sequence identities between GSTs of the same class they often display different substrate specificites. LÄS MER

  4. 4. Redesign of Alpha Class Glutathione Transferases to Study Their Catalytic Properties

    Författare :Lisa O Nilsson; Ralf Morgenstern; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Biochemistry; glutathione transferase; heterologous expression; heterodimer; hydroxyalkenal; protein redesign; sequential design; dimer-interface interactions; enzyme kinetics; glutathione; dynamic C-terminus; viscosity dependence; Biokemi; Biochemistry; Biokemi; biokemi; Biochemistry;

    Sammanfattning : A number of active site mutants of human Alpha class glutathione transferase A1-1 (hGST A1-1) were made and characterized to determine the structural determinants for alkenal activity. The choice of mutations was based on primary structure alignments of hGST A1-1 and the Alpha class enzyme with the highest alkenal activity, hGST A4-4, from three different species and crystal structure comparisons between the human enzymes. LÄS MER

  5. 5. Exploring amino-acid radicals and quinone redox chemistry in model proteins

    Författare :Kristina Westerlund; Cecilia Tommos; Astrid Gräslund; Sara Linse; Stockholms universitet; []
    Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; amino-acid radicals; quinone redox chemistry; model proteins; protein redesign; electrochemistry; Biochemistry; Biokemi; biokemi; Biochemistry;

    Sammanfattning : Amino-acid radical enzymes have been studied extensively for 30 years but the experimental barriers to determine the thermodynamic properties of their key radical cofactors are so challenging that only a handful of reports exist in the literature. This is a major drawback when trying to understand the long-range radical transfer and/or catalytic mechanisms of this important family of enzymes. LÄS MER