Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance.

Tooke, Catherine L; Hinchliffe, Philip; Bonomo, Robert A; Schofield, Christopher J; Mulholland, Adrian J; Spencer, James

Tooke, Catherine L; Hinchliffe, Philip; Bonomo, Robert A; Schofield, Christopher J; Mulholland, Adrian J; Spencer, James.

Afiliação

Tooke CL; School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom; Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, United Kingdom.
Hinchliffe P; School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.
Bonomo RA; Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA; Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; CWRU-Cleve
Schofield CJ; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom.
Mulholland AJ; Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol, United Kingdom.
Spencer J; School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom. Electronic address: Jim.Spencer@bristol.ac.uk.

J Biol Chem ; 296: 100126, 2021.

Article em En | MEDLINE | ID: mdl-33257320

Assuntos

Proteínas de Bactérias/química; Proteínas de Bactérias/metabolismo; Ceftazidima/farmacologia; Resistência Microbiana a Medicamentos; Klebsiella pneumoniae/enzimologia; Mutação; beta-Lactamases/química; beta-Lactamases/metabolismo; Acilação; Antibacterianos/farmacologia; Proteínas de Bactérias/genética; Domínio Catalítico; Hidrólise; Cinética; Klebsiella pneumoniae/efeitos dos fármacos; Klebsiella pneumoniae/genética; Modelos Moleculares; Mutagênese Sítio-Dirigida; Conformação Proteica; beta-Lactamases/genética

Palavras-chave

acylenzyme; antibiotic resistance; ceftazidime; crystal structure; enzyme catalysis; molecular dynamics; serine ß-lactamase; structurefunction; ß-lactam

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Beta-Lactamases / Resistência Microbiana a Medicamentos / Ceftazidima / Klebsiella pneumoniae / Mutação Idioma: En Ano de publicação: 2021 Tipo de documento: Article

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