scholarly journals Comparison of the Active-Site Design of Molybdenum Oxo-Transfer Enzymes by Quantum Mechanical Calculations

2014 ◽  
Vol 53 (22) ◽  
pp. 11913-11924 ◽  
Author(s):  
Jilai Li ◽  
Ulf Ryde
Keyword(s):  
Active Site ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Site Design ◽  
Oxo Transfer

scholarly journals Does the crystal structure of vanadium nitrogenase contain a reaction intermediate? Evidence from quantum refinement

2020 ◽  
Vol 25 (6) ◽  
pp. 847-861
Author(s):  
Lili Cao ◽  
Octav Caldararu ◽  
Ulf Ryde
Keyword(s):  
Crystal Structure ◽  
Active Site ◽  
Bound State ◽  
Real Space ◽  
Quantum Mechanical ◽  
Storage Site ◽  
Quantum Mechanical Calculations ◽  
Reaction Intermediate ◽  
Sulphide Ions ◽  
Vanadium Nitrogenase

Abstract Recently, a crystal structure of V-nitrogenase was presented, showing that one of the µ2 sulphide ions in the active site (S2B) is replaced by a lighter atom, suggested to be NH or NH2, i.e. representing a reaction intermediate. Moreover, a sulphur atom is found 7 Å from the S2B site, suggested to represent a storage site for this ion when it is displaced. We have re-evaluated this structure with quantum refinement, i.e. standard crystallographic refinement in which the empirical restraints (employed to ensure that the final structure makes chemical sense) are replaced by more accurate quantum–mechanical calculations. This allows us to test various interpretations of the structure, employing quantum–mechanical calculations to predict the ideal structure and to use crystallographic measures like the real-space Z-score and electron-density difference maps to decide which structure fits the crystallographic raw data best. We show that the structure contains an OH−-bound state, rather than an N2-derived reaction intermediate. Moreover, the structure shows dual conformations in the active site with ~ 14% undissociated S2B ligand, but the storage site seems to be fully occupied, weakening the suggestion that it represents a storage site for the dissociated ligand. Graphic abstract

scholarly journals Quantum Mechanical Study of Protonation of Oxygen Ligands in the Laccase Active Site Based on X-Ray Structures of Subatomic Resolution

2022 ◽  
Author(s):  
Sergei Gavryushov ◽  
Nikolay Kuzmich ◽  
Konstantin Polyakov
Keyword(s):  
Oxygen Reduction ◽  
Molecular Oxygen ◽  
High Precision ◽  
Active Site ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Stable States ◽  
Hydrogen Atoms ◽  
X Ray ◽  
Wide Range

Laccases are enzymes catalyzing oxidation of a wide range of organic and inorganic substrates accompanied by molecular oxygen reduction to water. Previously studies of oxygen reduction by laccases have recently been reported. They were based on single-crystal serial X-ray crystallography with increasing absorption doses at subatomic resolution, As a result, coordinates of all non-hydrogen atoms of the active site have been determined with high precision for both oxidized and reduced states of the enzyme. Those data can be used to clarify the mechanism of molecular oxygen reduction by laccases. However, the X-ray data lack information about protonation states of the oxygen ligands involved. Applying quantum mechanical calculations, in the present work protonation of oxygen ligands in the active site of laccase was determined for both reduced and oxidized states of the enzyme (the stable states observed in experiments at reduction of molecular oxygen in laccase). The high precision of X-ray-determined atom coordinates allowed us to simplify preliminary calculations of molecular mechanics for models used in the quantum mechanical calculations.

scholarly journals Structure and Function of NzeB, a Versatile C–C and C–N Bond Forming Diketopiperazine Dimerase

2020 ◽  
Author(s):  
Vikram V. Shende ◽  
Yogan Khatri ◽  
Sean A. Newmister ◽  
Jacob N. Sanders ◽  
Petra Lindovska ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cytochrome P450 ◽  
Active Site ◽  
Structure And Function ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Bond Forming ◽  
And Function ◽  
Insight Into

This report details the discovery and characterization of a versatile bacterial cytochrome P450, NzeB, which catalyzes the dimerization of diketopiperazines via enzymatic C–H functionalization. This includes the first high-resolution crystal structure of a diketopiperazine dimerase, which along with active site via mutagenesis and quantum mechanical calculations, provides insight into the selectivity and mechanism of these enzymes.

Structure and Function of NzeB, a Versatile C–C and C–N Bond Forming Diketopiperazine Dimerase

2020 ◽  
Author(s):  
Vikram V. Shende ◽  
Yogan Khatri ◽  
Sean A. Newmister ◽  
Jacob N. Sanders ◽  
Petra Lindovska ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Cytochrome P450 ◽  
Active Site ◽  
Structure And Function ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Bond Forming ◽  
And Function ◽  
Insight Into

This report details the discovery and characterization of a versatile bacterial cytochrome P450, NzeB, which catalyzes the dimerization of diketopiperazines via enzymatic C–H functionalization. This includes the first high-resolution crystal structure of a diketopiperazine dimerase, which along with active site via mutagenesis and quantum mechanical calculations, provides insight into the selectivity and mechanism of these enzymes.

scholarly journals Enzymatic control of dioxygen binding and functionalization of the flavin cofactor

2018 ◽  
Vol 115 (19) ◽  
pp. 4909-4914 ◽  
Author(s):  
Raspudin Saleem-Batcha ◽  
Frederick Stull ◽  
Jacob N. Sanders ◽  
Bradley S. Moore ◽  
Bruce A. Palfey ◽  
...  
Keyword(s):  
Active Site ◽  
Rational Design ◽  
Quantum Mechanical ◽  
Organic Substrates ◽  
Quantum Mechanical Calculations ◽  
Critical Transition ◽  
Precise Positioning ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fine Tune

The reactions of enzymes and cofactors with gaseous molecules such as dioxygen (O2) are challenging to study and remain among the most contentious subjects in biochemistry. To date, it is largely enigmatic how enzymes control and fine-tune their reactions with O2, as exemplified by the ubiquitous flavin-dependent enzymes that commonly facilitate redox chemistry such as the oxygenation of organic substrates. Here we employ O2-pressurized X-ray crystallography and quantum mechanical calculations to reveal how the precise positioning of O2 within a flavoenzyme’s active site enables the regiospecific formation of a covalent flavin–oxygen adduct and oxygenating species (i.e., the flavin-N5-oxide) by mimicking a critical transition state. This study unambiguously demonstrates how enzymes may control the O2 functionalization of an organic cofactor as prerequisite for oxidative catalysis. Our work thus illustrates how O2 reactivity can be harnessed in an enzymatic environment and provides crucial knowledge for future rational design of O2-reactive enzymes.

Crystal Forms of Semisynthetic Ergot Alkaloid Terguride

2002 ◽  
Vol 67 (4) ◽  
pp. 479-489 ◽  
Author(s):  
Michal Hušák ◽  
Bohumil Kratochvíl ◽  
Ivana Císařová ◽  
Ladislav Cvak ◽  
Alexandr Jegorov ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Ergot Alkaloid ◽  
Simplified Model ◽  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
X Ray Diffraction ◽  
Torsion Angles ◽  
Crystal Forms ◽  
X Ray ◽  
Independent Molecules

Two new structures of semisynthetic ergot alkaloid terguride created by unusual number of symmetry-independent molecules were determined by X-ray diffraction methods at 150 K. Form A (monoclinic, P212121, Z = 12) contains three symmetry-independent terguride molecules and two molecules of water in the asymmetric part of the unit cell. The form CA (monoclinic, P21, Z = 8) is an anhydrate remarkable by the presence of four symmetry-independent molecules in the crystal structure. Conformations of twelve symmetry-independent molecules that were found in four already described terguride structures are compared with torsion angles obtained by ab initio quantum-mechanical calculations for the simplified model of N-cyclohexyl-N'-diethylurea.

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