Stabilization of different types of transition states in a single enzyme active site: QM/MM analysis of enzymes in the alkaline phosphatase superfamily.

No abstract is available for this paper.

• Publication year

  2013

• Venue

  Journal of the American Chemical Society

• Publication date

  2013-07-09

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/ja403293dPMID 23786365PMCID PMC3759165
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer.

  2013cited by this paper
• Catalytic metal ion rearrangements underline promiscuity and evolvability of a metalloenzyme.

  2013cited by this paper
• Charging free energy calculations using the Generalized Solvent Boundary Potential (GSBP) and periodic boundary condition: a comparative analysis using ion solvation and oxidation free energy in proteins.

  2013cited by this paper
• Implementation of the solvent macromolecule boundary potential and application to model and realistic enzyme systems.

  2012cited by this paper
• Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

  2012cited by this paper
• Catalytic mechanism of aromatic prenylation by NphB.

  2012cited by this paper
• Catalytic promiscuity in Pseudomonas aeruginosa arylsulfatase as an example of chemistry‐driven protein evolution

  2012cited by this paper
• Examining the promiscuous phosphatase activity of Pseudomonas aeruginosa arylsulfatase: A comparison to analogous phosphatases

  2012cited by this paper
• Toward molecular models of proton pumping: Challenges, methods and relevant applications

  2012cited by this paper
• High-resolution analysis of Zn(2+) coordination in the alkaline phosphatase superfamily by EXAFS and x-ray crystallography.

  2012cited by this paper
• QM/MM studies of phosphoryl transfer reactions in Alkaline Phosphatase superfamily

  2012cited by this paper
• Application of Adaptive QM/MM Methods to Molecular Dynamics Simulations of Aqueous Systems.

  2012cited by this paper
• Simulations of allosteric motions in the zinc sensor CzrA.

  2012cited by this paper
• QM/MM analysis suggests that Alkaline Phosphatase (AP) and nucleotide pyrophosphatase/phosphodiesterase slightly tighten the transition state for phosphate diester hydrolysis relative to solution: implication for catalytic promiscuity in the AP superfamily.

  2012cited by this paper
• A modified QM/MM Hamiltonian with the Self-Consistent-Charge Density-Functional-Tight-Binding Theory for highly charged QM regions.

  2012cited by this paper
• Catalytic mechanism of RNA backbone cleavage by ribonuclease H from quantum mechanics/molecular mechanics simulations.

  2011cited by this paper
• Biological phosphoryl-transfer reactions: understanding mechanism and catalysis.

  2011cited by this paper
• DFTB3: Extension of the self-consistent-charge density-functional tight-binding method (SCC-DFTB).

  2011cited by this paper
• Promiscuity in alkaline phosphatase superfamily. Unraveling evolution through molecular simulations.

  2011cited by this paper
• Isotope-edited FTIR of alkaline phosphatase resolves paradoxical ligand binding properties and suggests a role for ground-state destabilization.

  2011cited by this paper
• Zinc chelation with hydroxamate in histone deacetylases modulated by water access to the linker binding channel.

  2011cited by this paper
• Paradynamics: an effective and reliable model for ab initio QM/MM free-energy calculations and related tasks.

  2011cited by this paper
• Reduction potentials and acidity constants of Mn superoxide dismutase calculated by QM/MM free-energy methods.

  2011cited by this paper
• Theoretical study of phosphodiester hydrolysis in nucleotide pyrophosphatase/phosphodiesterase. Environmental effects on the reaction mechanism.

  2010cited by this paper
• Including Charge Penetration Effects in Molecular Modeling.

  2010cited by this paper
• Analyzing protein structure and function using ancestral gene reconstruction.

  2010cited by this paper
• Free energy calculations using dual-level Born-Oppenheimer molecular dynamics.

  2010cited by this paper
• An implicit solvent model for SCC-DFTB with Charge-Dependent Radii.

  2010cited by this paper
• Recent progress in adaptive multiscale molecular dynamics simulations of soft matter.

  2010cited by this paper
• An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily

  2010cited by this paper
• Enzyme promiscuity: a mechanistic and evolutionary perspective.

  2010cited by this paper
• Electronic properties and desolvation penalties of metal ions plus protein electrostatics dictate the metal binding affinity and selectivity in the copper efflux regulator.

  2010cited by this paper
• A proton-shuttle reaction mechanism for histone deacetylase 8 and the catalytic role of metal ions.

  2010cited by this paper
• Mapping catalytic promiscuity in the alkaline phosphatase superfamily

  2009cited by this paper
• CHARMM: The biomolecular simulation program

  2009cited by this paper
• Quantum mechanical/molecular mechanical and density functional theory studies of a prototypical zinc peptidase (carboxypeptidase A) suggest a general acid-general base mechanism.

  2009cited by this paper
• Theoretical modeling of the reaction mechanism of phosphate monoester hydrolysis in alkaline phosphatase.

  2009cited by this paper
• Does water relay play an important role in phosphoryl transfer reactions? Insights from theoretical study of a model reaction in water and tert-butanol.

  2009cited by this paper
• The far reaches of enzymology.

  2009cited by this paper
• The hydrolysis activity of adenosine triphosphate in myosin: a theoretical analysis of anomeric effects and the nature of the transition state.

  2009cited by this paper
• Protein promiscuity and its implications for biotechnology

  2009cited by this paper
• Extensive conformational transitions are required to turn on ATP hydrolysis in myosin.

  2008cited by this paper
• Promiscuous sulfatase activity and thio-effects in a phosphodiesterase of the alkaline phosphatase superfamily.

  2008cited by this paper
• Comparative enzymology in the alkaline phosphatase superfamily to determine the catalytic role of an active-site metal ion.

  2008cited by this paper
• The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals

  2008cited by this paper
• On the interpretation of the observed linear free energy relationship in phosphate hydrolysis: a thorough computational study of phosphate diester hydrolysis in solution.

  2008cited by this paper
• Mechanistic study of protein phosphatase-1 (PP1), a catalytically promiscuous enzyme.

  2008cited by this paper
• Arginine coordination in enzymatic phosphoryl transfer: evaluation of the effect of Arg166 mutations in Escherichia coli alkaline phosphatase.

  2008cited by this paper
• Extension of the self-consistent-charge density-functional tight-binding method: third-order expansion of the density functional theory total energy and introduction of a modified effective coulomb interaction.

  2007cited by this paper
• SCC-DFTB: what is the proper degree of self-consistency?

  2007cited by this paper
• The reaction mechanism of paraoxon hydrolysis by phosphotriesterase from combined QM/MM simulations.

  2007cited by this paper
• Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions:  H, O, and P Atoms.

  2007cited by this paper
• Kinetic isotope effects for alkaline phosphatase reactions: implications for the role of active-site metal ions in catalysis.

  2007cited by this paper
• Enzyme promiscuity: mechanism and applications.

  2007cited by this paper
• Antibiotic deactivation by a dizinc beta-lactamase: mechanistic insights from QM/MM and DFT studies.

  2007cited by this paper
• pKa analysis for the zinc-bound water in human carbonic anhydrase II: Benchmark for "multiscale" QM/MM simulations and mechanistic implications.

  2007cited by this paper
• Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution.

  2006cited by this paper
• High-accuracy computation of reaction barriers in enzymes.

  2006cited by this paper
• Specific parametrisation of a hybrid potential to simulate reactions in phosphatases.

  2006cited by this paper
• Advances in methods and algorithms in a modern quantum chemistry program package.

  2006cited by this paper
• Alkaline phosphatase mono- and diesterase reactions: comparative transition state analysis.

  2006cited by this paper
• Development of effective quantum mechanical/molecular mechanical (QM/MM) methods for complex biological processes.

  2006cited by this paper
• Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release

  2006cited by this paper
• A critical evaluation of different QM/MM frontier treatments with SCC-DFTB as the QM method.

  2005cited by this paper
• Accurate QM/MM Free Energy Calculations of Enzyme Reactions:  Methylation by Catechol O-Methyltransferase.

  2005cited by this paper
• Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis.

  2005cited by this paper
• Improving the QM/MM Description of Chemical Processes:  A Dual Level Strategy To Explore the Potential Energy Surface in Very Large Systems.

  2005cited by this paper
• Reliable treatment of electrostatics in combined QM/MM simulation of macromolecules.

  2005cited by this paper
• Enhancing catalytic promiscuity for biocatalysis.

  2005cited by this paper
• Do electrostatic interactions with positively charged active site groups tighten the transition state for enzymatic phosphoryl transfer?

  2004cited by this paper
• Resurrecting ancient genes: experimental analysis of extinct molecules

  2004cited by this paper
• Modeling zinc in biomolecules with the self consistent charge‐density functional tight binding (SCC‐DFTB) method: Applications to structural and energetic analysis

  2003cited by this paper
• Ab Initio QM/MM Simulation with Proper Sampling: “First Principle” Calculations of the Free Energy of the Autodissociation of Water in Aqueous Solution

  2002cited by this paper
• Optimization of quantum mechanical molecular mechanical partitioning schemes: Gaussian delocalization of molecular mechanical charges and the double link atom method

  2002cited by this paper
• Quantum dynamics of hydride transfer catalyzed by bimetallic electrophilic catalysis: synchronous motion of Mg(2+) and H(-) in xylose isomerase.

  2002cited by this paper
• Triosephosphate isomerase: a theoretical comparison of alternative pathways.

  2001cited by this paper
• Functional interrelationships in the alkaline phosphatase superfamily: phosphodiesterase activity of Escherichia coli alkaline phosphatase.

  2001cited by this paper
• Conserved core structure and active site residues in alkaline phosphatase superfamily enzymes

  2001cited by this paper
• A QM/MM Implementation of the Self-Consistent Charge Density Functional Tight Binding (SCC-DFTB) Method

  2001cited by this paper
• Generalized solvent boundary potential for computer simulations

  1999cited by this paper
• Optimized atomic radii for protein continuum electrostatics solvation forces.

  1999cited by this paper
• Catalytic promiscuity and the evolution of new enzymatic activities.

  1999cited by this paper
• Does the Active Site Arginine Change the Nature of the Transition State for Alkaline Phosphatase-Catalyzed Phosphoryl Transfer?

  1999cited by this paper
• Mechanistic alternatives in phosphate monoester hydrolysis: what conclusions can be drawn from available experimental data?

  1999cited by this paper
• SULFATASE ACTIVITY OF E. COLI ALKALINE PHOSPHATASE DEMONSTRATES A FUNCTIONAL LINK TO ARYLSULFATASES, AN EVOLUTIONARILY RELATED ENZYME FAMILY

  1998cited by this paper
• Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson-Boltzmann equation

  1998cited by this paper
• A superfamily of metalloenzymes unifies phosphopentomutase and cofactor‐independent phosphoglycerate mutase with alkaline phosphatases and sulfatases

  1998cited by this paper
• All-atom empirical potential for molecular modeling and dynamics studies of proteins.

  1998cited by this paper
• Atomic Radii for Continuum Electrostatics Calculations Based on Molecular Dynamics Free Energy Simulations

  1997cited by this paper
• New spherical‐cutoff methods for long‐range forces in macromolecular simulation

  1994cited by this paper
• Density-functional thermochemistry. III. The role of exact exchange

  1993cited by this paper
• THE weighted histogram analysis method for free‐energy calculations on biomolecules. I. The method

  1992cited by this paper
• Solvent effects on protein motion and protein effects on solvent motion. Dynamics of the active site region of lysozyme.

  1989cited by this paper
• Polar hydrogen positions in proteins: Empirical energy placement and neutron diffraction comparison

  1988cited by this paper
• Density-functional exchange-energy approximation with correct asymptotic behavior.

  1988cited by this paper
• Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density.

  1988cited by this paper
• A complete basis set model chemistry. I. The total energies of closed‐shell atoms and hydrides of the first‐row elements

  1988cited by this paper
• Deformable stochastic boundaries in molecular dynamics

  1983cited by this paper
• Comparison of simple potential functions for simulating liquid water

  1983cited by this paper
• CHARMM: A program for macromolecular energy, minimization, and dynamics calculations

  1983cited by this paper

• Recruitment of Enzymatic Labels via Glycan-Lectin Interactions for Electrochemical Immunosensing of Anti-dsDNA Antibodies.

  2026cites this paper
• Catching CRISPR-Cas9 in Action.

  2025cites this paper
• Force fields matter in DNA pol η mechanistic analysis

  2025cites this paper
• Computational and experimental identification of an exceptionally efficient ethyl ester synthetase with broad substrate specificity and high product yield, suggests potential for industrial biocatalysis.

  2024cites this paper
• Unusual commonality in active site structural features of substrate promiscuous and specialist enzymes.

  2022cites this paper
• One-Step Determination of Alkaline Phosphatase in Human Serum Based on Manganese (IV) Dioxide/Manganese (II)-Mediated Nuclear Magnetic Resonance (NMR) Relaxation

  2022cites this paper
• Multiscale Workflow for Modeling Ligand Complexes of Zinc Metalloproteins

  2021cites this paper
• Structures of an engineered phospholipase D with specificity for secondary alcohol transphosphatidylation: insights into plasticity of substrate binding and activation

  2021cites this paper
• Key features of magnesium that underpin its role as the major ion for electrophilic biocatalysis

  2020cites this paper
• Detection and beyond: challenges and advances in aptamer-based biosensors

  2020cites this paper
• Near-infrared ratiometric probe with a self-immolative spacer for rapid and sensitive detection of alkaline phosphatase activity and imaging in vivo.

  2020cites this paper
• Differences in the Nature of the Phosphoryl Transfer Transition State in Protein Phosphatase 1 and Alkaline Phosphatase: Insights from QM Cluster Models.

  2020cites this paper
• Activatable Off-on Near-Infrared QCy7-based Fluorogenic Probes for Bioimaging.

  2020cites this paper
• One- and Two- Proton Transfer Mechanisms Coexist in One Active Site.

  2020cites this paper
• The catalytic mechanism of S-acyltransferases: acylation is triggered on by a loose transition state and deacylation is turned off by a tight transition state.

  2019cites this paper
• Near-infrared mito-specific fluorescent probe for ratiometric detection and imaging of alkaline phosphatase activity with high sensitivity.

  2019cites this paper
• Thermodynamically and Kinetically Controlled Reactions in Biocatalysis – from Concepts to Perspectives

  2019cites this paper
• Extensive free-energy simulations identify water as the base in nucleotide addition by DNA polymerase

  2019cites this paper
• Steering the lipid transfer to unravel the mechanism of CETP inhibition.

  2019cites this paper
• Non-Conventional Metal Ion Cofactor Requirement of Dinoflagellate Alkaline Phosphatase and Translational Regulation by Phosphorus Limitation

  2019influential citation
• A high-sensitivity fluorescent probe with a self-immolative spacer for real-time ratiometric detection and imaging of alkaline phosphatase activity

  2019cites this paper
• Fluorogenic probes for disease-relevant enzymes.

  2019cites this paper
• Computer simulations of the catalytic mechanism of wild-type and mutant β-phosphoglucomutase.

  2018cites this paper
• QM/MM free energy simulations of the reaction catalysed by (4S)-limonene synthase involving linalyl diphosphate (LPP) substrate

  2018cites this paper
• Fast and sensitive near-infrared fluorescent probes for ALP detection and 3d printed calcium phosphate scaffold imaging in vivo.

  2018cites this paper
• Analysis of Phosphoryl-Transfer Enzymes with QM/MM Free Energy Simulations.

  2018cites this paper
• Challenges and advances in the computational modeling of biological phosphate hydrolysis.

  2018cites this paper
• Thermodynamics of Reactions Affected by Medium Reorganization.

  2018cites this paper
• Transition State Interactions in a Promiscuous Enzyme: Sulfate and Phosphate Monoester Hydrolysis by Pseudomonas aeruginosa Arylsulfatase

  2018cites this paper
• Quantum Mechanical/Molecular Mechanical Analysis of the Catalytic Mechanism of Phosphoserine Phosphatase

  2018cites this paper
• Cooperativity and flexibility in enzyme evolution.

  2018cites this paper
• Laboratory evolution of protein conformational dynamics.

  2018cites this paper
• Water is an active matrix of life for cell and molecular biology

  2017cites this paper
• Functional Analysis of Early Core Region Modification in the LPS of Gram-negative Bacteria

  2017cites this paper
• Understanding the Catalytic Mechanism and the Nature of the Transition State of an Attractive Drug-Target Enzyme (Shikimate Kinase) by Quantum Mechanical/Molecular Mechanical (QM/MM) Studies.

  2017cites this paper
• Using Empirical Valence Bond Constructs as Reference Potentials For High‐Level Quantum Mechanical Calculations

  2017cites this paper
• Understanding the Catalytic Mechanism and the Substrate Specificity of an Engineered Gluten Hydrolase by QM/MM Molecular Dynamics and Free Energy Simulations

  2017cites this paper
• Studies in bacterial phosphotriesterase evolution, dynamics, and engineering

  2017cites this paper
• Regulation and Plasticity of Catalysis in Enzymes: Insights from Analysis of Mechanochemical Coupling in Myosin.

  2017cites this paper
• A Self-Activated Mechanism for Nucleic Acid Polymerization Catalyzed by DNA/RNA Polymerases.

  2016cites this paper
• Promiscuity in the Enzymatic Catalysis of Phosphate and Sulfate Transfer

  2016cites this paper
• QM/MM Analysis of Transition States and Transition State Analogues in Metalloenzymes.

  2016cites this paper
• Theoretical Proposal for the Whole Phosphate Diester Hydrolysis Mechanism Promoted by a Catalytic Promiscuous Dinuclear Copper(II) Complex.

  2016cites this paper
• Semiempirical Quantum Mechanical Methods for Noncovalent Interactions for Chemical and Biochemical Applications

  2016cites this paper
• QM/MM free energy simulations: recent progress and challenges

  2016cites this paper
• A multiscale computational approach to study RNase A catalysis

  2016cites this paper
• Determination of Precise Redox Properties of Oxygen-Doped Single-Walled Carbon Nanotubes Based on in Situ Photoluminescence Electrochemistry

  2016cites this paper
• Promiscuity and electrostatic flexibility in the alkaline phosphatase superfamily.

  2016influential citation
• Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP.

  2016cites this paper
• Anthrax Edema Factor: An Ion-Adaptive Mechanism of Catalysis with Increased Transition-State Conformational Flexibility.

  2016cites this paper
• Leaving Group Ability Observably Affects Transition State Structure in a Single Enzyme Active Site.

  2016cites this paper
• Substrate and Transition State Binding in Alkaline Phosphatase Analyzed by Computation of Oxygen Isotope Effects.

  2016cites this paper
• The ONIOM Method and Its Applications.

  2015cites this paper
• Structural and computational dissection of the catalytic mechanism of the inorganic pyrophosphatase from Mycobacterium tuberculosis.

  2015cites this paper
• Phosphate Hydrolysis by the Fe2-Ca3-Dependent Alkaline Phosphatase PhoX: Mechanistic Insights from DFT calculations.

  2015cites this paper
• DFTB3 Parametrization for Copper: The Importance of Orbital Angular Momentum Dependence of Hubbard Parameters

  2015cites this paper
• QM/MM Simulations of Amyloid-β 42 Degradation by IDE in the Presence and Absence of ATP

  2015cites this paper
• A comparative study of trypsin specificity based on QM/MM molecular dynamics simulation and QM/MM GBSA calculation

  2015cites this paper
• Substrate-Assisted Catalysis in the Reaction Catalyzed by Salicylic Acid Binding Protein 2 (SABP2), a Potential Mechanism of Substrate Discrimination for Some Promiscuous Enzymes.

  2015cites this paper
• Classical And Ab Initio Qm/mm Simulations Of Bacterial Enzymes

  2015cites this paper
• Theoretical Study of the Free Energy Surface and Kinetics of the Hepatitis C Virus NS3/NS4A Serine Protease Reaction with the NS5A/5B Substrate. Does the Generally Accepted Tetrahedral Intermediate Really Exist?

  2015cites this paper
• Cooperative Electrostatic Interactions Drive Functional Evolution in the Alkaline Phosphatase Superfamily

  2015cites this paper
• Multiscale methods for computational RNA enzymology.

  2015cites this paper
• A ratiometric fluorescent probe for in vivo tracking of alkaline phosphatase level variation resulting from drug-induced organ damage.

  2015cites this paper
• A fluorescent probe for alkaline phosphatase via excited state intramolecular proton transfer

  2015cites this paper
• The reaction mechanism of UDP-GlcNAc 5,6-dehydratase: a quantum mechanical/molecular mechanical (QM/MM) study

  2014cites this paper
• Quantum mechanical/molecular mechanical studies of zinc hydrolases

  2014cites this paper
• Density functional tight binding: values of semi-empirical methods in an ab initio era.

  2014cites this paper
• Comparison of ab Initio, DFT, and Semiempirical QM/MM Approaches for Description of Catalytic Mechanism of Hairpin Ribozyme.

  2014cites this paper
• Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis

  2014cites this paper
• The phosphatase mechanism of bifunctional kinase/phosphatase AceK.

  2014cites this paper
• Mechanismic investigation on the cleavage of phosphate monoester catalyzed by unsymmetrical macrocyclic dinuclear complexes: the selection of metal centers and the intrinsic flexibility of the ligand.

  2014cites this paper
• Phosphate monoester hydrolysis by trinuclear alkaline phosphatase; DFT study of transition States and reaction mechanism.

  2014cites this paper
• Molecular Simulation of Water and Hydration Effects in Different Environments: Challenges and Developments for DFTB Based Models

  2014cites this paper
• Ab Initio QM/MM Study Shows a Highly Dissociated SN2 Hydrolysis Mechanism for the cGMP-Specific Phosphodiesterase-5.

  2014cites this paper
• Parametrization of DFTB3/3OB for Magnesium and Zinc for Chemical and Biological Applications

  2014cites this paper
• Parameterization of DFTB3/3OB for Sulfur and Phosphorus for Chemical and Biological Applications

  2014cites this paper
• Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference Potential while Retaining Accuracy of the Target Fine Model

  2014cites this paper
• Catalytic activity of human placental alkaline phosphatase (PLAP): insights from a computational study.

  2014cites this paper