scholarly journals The Reaction Path of Product Release in NO Detoxification at the Active Site of Truncated Hemoglobin N in MCSCF Approach

2020 ◽  
Vol 15 (2) ◽  
pp. 172-179
Author(s):  
K.V. Simon ◽  
A.V. Tulub
Keyword(s):  
Active Site ◽  
Geometry Optimization ◽  
Molecular Orbitals ◽  
Water Molecules ◽  
Nitrate Anion ◽  
Reaction Products ◽  
Truncated Hemoglobin ◽  
Localized Molecular Orbitals ◽  
Self Consistent Field ◽  
Full Interaction

The Multi-Configurational Self-Consistent Field approach with the geometry optimization was applied to the calculation of electronic properties of active site of heme core of truncated hemoglobin N, with the inclusion of [ONOO] functional group and two water molecules. The localized molecular orbitals are employed as a starting set. Two subspaces of full interaction have been used by the construction of MCSCF wavefunction. The first one includes 3d orbitals of iron atom, and the second contains bonding and antibonding molecular orbitals of peroxynitrite with one unshared electronic pair of the O2 fragment. The reaction is characterized by two transition states; the products are nitrate anion and one unbound water molecule. There arise an evidence of NO2 and NO radicals as the reaction products.

scholarly journals Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 22 ◽  
Author(s):  
Ignacio Boron ◽  
Juan Pablo Bustamante ◽  
Kelly S Davidge ◽  
Sandip Singh ◽  
Lesley AH Bowman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Active Site ◽  
Water Molecules ◽  
Single Mutation ◽  
Truncated Hemoglobin ◽  
Kinetic Measurements ◽  
Migration Rates ◽  
Ligand Migration ◽  
Site Water ◽  
Dynamics Simulations

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels that are partially blocked by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations introduce modifications in both tunnel topologies and affect the incoming ligand capacity to displace retained water molecules at the active site. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

scholarly journals Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 22 ◽  
Author(s):  
Ignacio Boron ◽  
Juan Pablo Bustamante ◽  
Kelly S Davidge ◽  
Sandip Singh ◽  
Lesley AH Bowman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Active Site ◽  
Water Molecules ◽  
Single Mutation ◽  
Truncated Hemoglobin ◽  
Kinetic Measurements ◽  
Migration Rates ◽  
Ligand Migration ◽  
Site Water ◽  
Dynamics Simulations

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

Simple theoretical models for elimination reactions on polar catalysts; The reactivity of halogeno-, hydroxy-, amino- and mercaptopropane

1982 ◽  
Vol 47 (8) ◽  
pp. 2180-2189 ◽  
Author(s):  
Jiří Sedláček
Keyword(s):  
Theoretical Models ◽  
Molecular Orbitals ◽  
Localized Molecular Orbitals ◽  
Hydroxy Amino ◽  
Elimination Reactions ◽  
Simple Models

CNDO/2 calculations have been made for simple models of the adsorption of (CH3)2CHZ molecules (Z = Cl, OH, NH2, and SH) on the surface of polar catalysts. The results of these calculations and their interpretation by the method of configuration analysis in terms of uniformly localized molecular orbitals made it possible to explain satisfactorily a series of experimental facts. The mechanism and stereoselectivity of the reaction as well as reactivity trends for the series of the molecules studied are discussed.

Unitary Optimization of Localized Molecular Orbitals

2013 ◽  
Vol 9 (12) ◽  
pp. 5365-5372 ◽  
Author(s):  
Susi Lehtola ◽  
Hannes Jónsson
Keyword(s):  
Molecular Orbitals ◽  
Localized Molecular Orbitals
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