A combined computational and experimental study on selective flucloxacillin hydroxylation by cytochrome P450 BM3 variants.

[1]  P. Grootenhuis,et al.  Efficient Screening of Cytochrome P450 BM3 Mutants for Their Metabolic Activity and Diversity toward a Wide Set of Drug-Like Molecules in Chemical Space , 2011, Drug Metabolism and Disposition.

[2]  Chris Oostenbrink,et al.  Improved ligand-protein binding affinity predictions using multiple binding modes. , 2010, Biophysical journal.

[3]  R. Hultcrantz,et al.  Liver damage from flucloxacillin, cloxacillin and dicloxacillin. , 1992, Journal of hepatology.

[4]  Elaine Holmes,et al.  Heteronuclear 19F-1H statistical total correlation spectroscopy as a tool in drug metabolism: study of flucloxacillin biotransformation. , 2008, Analytical chemistry.

[5]  J. Wichard,et al.  Comprehensive and Automated Linear Interaction Energy Based Binding-Affinity Prediction for Multifarious Cytochrome P450 Aromatase Inhibitors , 2017, J. Chem. Inf. Model..

[6]  H. Jick,et al.  Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: cohort study using data from the UK General Practice Research Database. , 2005, British journal of clinical pharmacology.

[7]  N. Vermeulen,et al.  The role of protein plasticity in computational rationalization studies on regioselectivity in testosterone hydroxylation by cytochrome P450 BM3 mutants. , 2012, Current drug metabolism.

[8]  Ben M. Webb,et al.  Comparative Protein Structure Modeling Using MODELLER , 2007, Current protocols in protein science.

[9]  Vlada B Urlacher,et al.  Screening of a minimal enriched P450 BM3 mutant library for hydroxylation of cyclic and acyclic alkanes. , 2011, Chemical communications.

[10]  A. Thunnissen,et al.  Structural basis of steroid binding and oxidation by the cytochrome P450 CYP109E1 from Bacillus megaterium , 2016, The FEBS journal.

[11]  Lars Ridder,et al.  Mechanism and structure-reactivity relationships for aromatic hydroxylation by cytochrome P450. , 2004, Organic & biomolecular chemistry.

[12]  Thomas E. Cheatham,et al.  Quantum mechanically derived AMBER‐compatible heme parameters for various states of the cytochrome P450 catalytic cycle , 2012, J. Comput. Chem..

[13]  Junmei Wang,et al.  Development and testing of a general amber force field , 2004, J. Comput. Chem..

[14]  P. Kollman,et al.  Automatic atom type and bond type perception in molecular mechanical calculations. , 2006, Journal of molecular graphics & modelling.

[15]  P. Ortiz de Montellano,et al.  Catalytic Activities of Tumor-Specific Human Cytochrome P450 CYP2W1 Toward Endogenous Substrates , 2016, Drug Metabolism and Disposition.

[16]  F. Arnold,et al.  Catalysts on Demand: Selective Oxidations by Laboratory-Evolved Cytochrome P450 BM3 , 2009 .

[17]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[18]  Chris Oostenbrink,et al.  Computational prediction of drug binding and rationalisation of selectivity towards cytochromes P450 , 2008 .

[19]  P. T. ter Horst,et al.  Development and validation of a liquid chromatography/tandem mass spectrometry method for the quantification of flucloxacillin and cloxacillin in microdialysis samples. , 2014, Biomedical chromatography : BMC.

[20]  P450BM3 on Steroids: The Swiss Army Knife P450 Enzyme Just Gets Better , 2011, Chembiochem : a European journal of chemical biology.

[21]  Flucloxacillin , 2020, Reactions Weekly.

[22]  N. Vermeulen,et al.  Identification of critical residues in novel drug metabolizing mutants of cytochrome P450 BM3 using random mutagenesis. , 2007, Journal of medicinal chemistry.

[23]  S. Wijmenga,et al.  Active site substitution A82W improves the regioselectivity of steroid hydroxylation by cytochrome P450 BM3 mutants as rationalized by spin relaxation nuclear magnetic resonance studies. , 2012, Biochemistry.

[24]  Nico P E Vermeulen,et al.  Application of engineered cytochrome P450 mutants as biocatalysts for the synthesis of benzylic and aromatic metabolites of fenamic acid NSAIDs. , 2014, Bioorganic & medicinal chemistry.

[25]  Lars Olsen,et al.  Insights into regioselective metabolism of mefenamic acid by cytochrome P450 BM3 mutants through crystallography, docking, molecular dynamics, and free energy calculations , 2016, Proteins.

[26]  N. Vermeulen,et al.  Application of drug metabolising mutants of cytochrome P450 BM3 (CYP102A1) as biocatalysts for the generation of reactive metabolites. , 2008, Chemico-biological interactions.

[27]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[28]  M. Daly,et al.  HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin , 2009, Nature Genetics.

[29]  Chris Morley,et al.  Open Babel: An open chemical toolbox , 2011, J. Cheminformatics.

[30]  Thomas Stützle,et al.  An ant colony optimization approach to flexible protein–ligand docking , 2007, Swarm Intelligence.

[31]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[32]  Andrej Sali,et al.  Comparative Protein Structure Modeling Using MODELLER , 2014, Current protocols in bioinformatics.

[33]  E. Björnsson,et al.  Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden , 2005, Scandinavian journal of gastroenterology.

[34]  A. Munro,et al.  Roles of key active-site residues in flavocytochrome P450 BM3. , 1999, The Biochemical journal.

[35]  Robert A. Copeland,et al.  Enzymes: A Practical Introduction to Structure, Mechanism, and Data Analysis , 1996 .

[36]  N. Vermeulen,et al.  Heterotropic and homotropic cooperativity by a drug-metabolising mutant of cytochrome P450 BM3. , 2006, Biochemical and biophysical research communications.

[37]  S. D. Beer,et al.  Regio‐ and Stereoselective Hydroxylation of Optically Active α‐Ionone Enantiomers by Engineered Cytochrome P450 BM3 Mutants , 2012 .

[38]  L. Wong,et al.  Protein engineering of Bacillus megaterium CYP102. The oxidation of polycyclic aromatic hydrocarbons. , 2001, European journal of biochemistry.

[39]  T. Ost,et al.  Rational re‐design of the substrate binding site of flavocytochrome P450 BM3 , 2000, FEBS letters.

[40]  Mark S. Gordon,et al.  General atomic and molecular electronic structure system , 1993, J. Comput. Chem..

[41]  G. Rolinson,et al.  Flucloxacillin, a New Isoxazolyl Penicillin, Compared with Oxacillin, Cloxacillin, and Dicloxacillin , 1970, British medical journal.

[42]  Christine M. Bathelt,et al.  Quantum Mechanics/Molecular Mechanics Modeling of Regioselectivity of Drug Metabolism in Cytochrome P450 2C9 , 2013, Journal of the American Chemical Society.

[43]  R. J. Kenny,et al.  Evolved CYP102A1 (P450BM3) variants oxidise a range of non-natural substrates and offer new selectivity options. , 2008, Chemical communications.

[44]  M. Pirmohamed,et al.  Characterisation of flucloxacillin and 5‐hydroxymethyl flucloxacillin haptenated HSA in vitro and in vivo , 2009, Proteomics. Clinical applications.

[45]  Gheorghe-Doru Roiban,et al.  Achieving Regio‐ and Enantioselectivity of P450‐Catalyzed Oxidative CH Activation of Small Functionalized Molecules by Structure‐Guided Directed Evolution , 2012, Chembiochem : a European journal of chemical biology.

[46]  Frances H Arnold,et al.  Cytochrome P450: taming a wild type enzyme. , 2011, Current opinion in biotechnology.

[47]  P. Balladur,et al.  Indirect cytotoxicity of flucloxacillin toward human biliary epithelium via metabolite formation in hepatocytes. , 2001, Chemical research in toxicology.

[48]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997, J. Comput. Chem..

[49]  Adrian J Mulholland,et al.  Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450 , 2011, Proceedings of the National Academy of Sciences.

[50]  M. Pirmohamed,et al.  Human leukocyte antigen (HLA)‐B*57:01‐restricted activation of drug‐specific T cells provides the immunological basis for flucloxacillin‐induced liver injury , 2013, Hepatology.

[51]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[52]  Chris Oostenbrink,et al.  Free Energy Calculations Give Insight into the Stereoselective Hydroxylation of α-Ionones by Engineered Cytochrome P450 BM3 Mutants , 2012, J. Chem. Inf. Model..

[53]  T. Omura,et al.  THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. II. SOLUBILIZATION, PURIFICATION, AND PROPERTIES. , 1964, The Journal of biological chemistry.

[54]  R. Dror,et al.  Improved side-chain torsion potentials for the Amber ff99SB protein force field , 2010, Proteins.

[55]  Andreas Bender,et al.  Computational Prediction of Metabolism: Sites, Products, SAR, P450 Enzyme Dynamics, and Mechanisms , 2012, J. Chem. Inf. Model..

[56]  T. Omura,et al.  THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. , 1964, The Journal of biological chemistry.

[57]  Chris Oostenbrink,et al.  Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking. , 2006, Journal of medicinal chemistry.

[58]  T. Halgren Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94 , 1996, J. Comput. Chem..

[59]  Thomas Stützle,et al.  Empirical Scoring Functions for Advanced Protein-Ligand Docking with PLANTS , 2009, J. Chem. Inf. Model..

[60]  A W Munro,et al.  Flavocytochrome P450 BM3: an update on structure and mechanism of a biotechnologically important enzyme. , 2005, Biochemical Society transactions.