The Role of Mutations at the Side Door on the Thermal Stability and Structural Flexibility of the pnbCE Enzyme
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Habib U. Rehman
und
Steven R. Gwaltney
Abstract
We have investigated the role of a specific gate residue, LEU362, located at the side-door of the pnbCE enzyme, on the thermal stability and structural flexibility of the enzyme. pnbCE is a bacterial carboxylesterase enzyme from Bacillus subtilis, which has a structural resemblance as well as similar catalytic behavior to the mammalian carboxylesterases. Mutations at the side-door residue 362 of pnbCE are known to alter the catalytic activity of this enzyme. Using molecular dynamics simulations at several temperatures, we have studied the mechanism through which mutations at position 362 of pnbCE affect the structure and dynamics of this enzyme. We have identified two coil residues, SER218 and GLN276, whose interactions with residue 362 in wild-type and mutant pnbCE enzymes control the dynamics of the side-door domain of pnbCE. A hydrogen bond between the GLN276 and ARG362 residues in the arginine substituted (L362R) pnbCE mutant enzyme appears to be responsible for locking the side-door domain region of the L362R enzyme, thus lowering the catalytic rates of the L362R mutant pnbCE enzyme compared to the wild-type. Similarly, a hydrogen bond formed between SER218 and ARG362 in L362R provides thermal stability to the arginine substituted mutant enzyme. This hydrogen bond is not as prevalent in the wild-type or other mutated pnbCE's, making them more prone to structural fluctuations upon increasing temperature. A trade-off between thermal stability of pnbCE and flexibility of the side-door domain region appears to be a best compromise for effectively controlling the catalytic properties of mutated pnbCE enzymes.
Acknowledgement
This work was supported in part by the National Science Foundation under award numbers EPS 0903787 and EPS 1006883.
©2016 Walter de Gruyter Berlin/Boston
Artikel in diesem Heft
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- Preface
- Congratulations to Michael Springborg
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Artikel in diesem Heft
- Frontmatter
- Preface
- Congratulations to Michael Springborg
- Fourier Space Uncoupled Hartree–Fock Polarizabilities of One-Dimensionally Periodic Systems. Polyethylene and Polysilane Revisited
- Construction of Constrained Dipole Oscillator Strength Distributions
- Incremental DF-LCCSD(T) Calculations for a Water Molecule Inside and Outside Armchair Carbon Nanotubes
- An Efficient Unrestricted PCM-Elongation Method for Large High-Spin Polymer/Dendrimer Systems
- Variable van der Waals Radii Derived From a Hybrid Gaussian Charge Distribution Model for Continuum-Solvent Electrostatic Calculations
- Natural Extension of Hartree–Fock Through Extremal 1-Fermion Information: Overview and Application to the Lithium Atom
- Direct Piezoelectric Tensor of 3D Periodic Systems through a Coupled Perturbed Hartree–Fock/Kohn–Sham Method
- Intensive Atomization Energy: Re-Thinking a Metric for Electronic Structure Theory Methods
- The VES Hypothesis and Protein Conformational Changes
- Understanding the Electronic Structure of Graphene Quantum Dot-Fullerene Nanohybrids for Photovoltaic Applications
- A First-Principles Study of Metal-Decorated Graphene Nanoribbons for Hydrogen Storage
- Defect Effects on the Interfacial Interactions between a (5, 5) Carbon Nanotube and an Al (111) Surface
- Structural Insight into Self Assembly of Sophorolipids: A Molecular Dynamics Simulation Study
- The Role of Mutations at the Side Door on the Thermal Stability and Structural Flexibility of the pnbCE Enzyme
- Electric (Hyper) Polarizability of the Hypofluorous Acid (HOF) from High-Level ab initio Calculations with Especially Designed Purpose-Oriented Basis Sets
- Conformational and Vibrational Analysis of 2-, 3- and 4-Pyridinecarbonyl Chloride Using DFT
- Spectral Properties of α and β L Rhamno-Indigo Molecules and Activities Prediction Through NBO Analysis. A DFT Study
- Solid State Structure Prediction Through DFT Calculations and 13C NMR Measurements: Case Study of Spiro-2,4-dithiohydantoins
- Eu2+-Containing Luminescent Perovskite-Type Hydrides Studied by Electron Paramagnetic Resonance
- Mn Adsorption on the GaAs(111)–(2×2)B Surface: First Principles Studies
- Charge and Compositional Effects on the 2D–3D Transition in Octameric AgAu Clusters
- Diversity Characterization of Binary Clusters by Means of a Generalized Distance
- First Principle Investigation of (Bi2O3)n Clusters With n = 6 − 9
- The Role of Aluminum Substitution on the Stability of Substituted Polyhedral Oligomeric Silsesquioxanes
- Ab-Initio Investigation of Nowotny Chimney Ladder Silicide Os2Si3 Using the Modified BJ Potential
- Surface Plasmon Assisted Two-Photon Ionization of Noble and Alkali Metal Clusters
- Temperature Dependence of Stability of Copper Clusters
- Detecting and Quantifying Geometric Features in Large Series of Cluster Structures
