English
norskBlar i forfatter "Skagseth, Susann"
Viser treff 1-9 av 9
-
Computational design of the temperature optimum of an enzyme reaction
(Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-28)Cold-adapted enzymes are characterized both by a higher catalytic activity at low temperatures and by having their temperature optimum down-shifted, compared to mesophilic orthologs. In several cases, the optimum does not coincide with the onset of protein melting but reflects some other type of inactivation. In the psychrophilic α-amylase from an Antarctic bacterium, the inactivation is thought to ... -
Investigating the role of residues W228 and Y233 in the structure and activity of the GIM-1 metallo-beta-lactamase.
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-12-07)Metallo--lactamases (MBLs) hydrolyze virtually all -lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs. The GIM-1 active-site ... -
Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters
(Journal article; Tidsskriftartikkel; Peer reviewed, 2022-01-25)Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain-contrary to earlier predictions-a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance ... -
Metallo-β-lactamase inhibitors by bioisosteric replacement: preparation, activity and binding
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-04-14)Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent ... -
Mutational, structural and inhibitory investigations of metallo-β-lactamases involved in antibiotic resistance
(Doctoral thesis; Doktorgradsavhandling, 2017-02-16)This thesis focuses on metallo-β-lactamases (MBLs) enzymes that break down a wide variety of antibiotics. Bacteria harboring genes expressing MBLs are antibiotic resistant. If the MBL genes are found on mobile genetic elements, the spread of the genes between bacteria becomes easier. To date, there are no MBL inhibitors available for blocking the enzyme activity, and thus there is an urgent need to ... -
Site-directed mutagenesis of the metallo-β-lactamase VIM-7 from the opportunistic human pathogenic bacteria Pseudomonas aeruginosa
(Master thesis; Mastergradsoppgave, 2012-05-15)The metallo-β-lactamases (MBLs) are enzymes with the ability to hydrolyse the β-lactam antibiotics. The worldwide emergence of the antibiotic resistant MBLs poses an increasing clinical threat. The VIM enzymes are a growing family of carbapenemases with a wide geographic distribution in Europe, South America and the USA. The VIM-7, the first VIM enzyme to be discovered in the USA, is the most divergent ... -
Structural insights into TMB-1 and the role of residues 119 and 228 in substrate and inhibitor binding
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-30)Metallo-β-lactamases (MBLs) threaten the effectiveness of β-lactam antibiotics, including carbapenems, and are a concern for global public health. β-Lactam/β-lactamase inhibitor combinations active against class A and class D carbapenemases are used, but no clinically useful MBL inhibitor is currently available. Tripoli metallo-β-lactamase-1 (TMB-1) and TMB-2 are members of MBL subclass B1a, where ... -
Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-β-lactamases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-18)Metallo-β-lactamases (MBLs) are an emerging cause of bacterial antibiotic resistance by hydrolysing all classes of β-lactams except monobactams, and the MBLs are not inhibited by clinically available serine-β-lactamase inhibitors. Two of the most commonly encountered MBLs in clinical isolates worldwide – the New Delhi metallo-β-lactamase (NDM-1) and the Verona integron-encoded metallo-β-lactamase ... -
ZN148 Is a Modular Synthetic Metallo-beta-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-21)Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, ...
