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Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2

Mariya Grigor'evna Khrenova 1, 2
Mariya Grigor'evna Khrenova
, 
Alexander Vladimirovich Nemukhin 2, 3
Alexander Vladimirovich Nemukhin
, 
Vladinir Grigor'evich Tsirelson 4
Vladinir Grigor'evich Tsirelson
10.1016/j.mencom.2020.09.010
Published 2020-08-31
Communication , Volume 30, Issue 5, 583-585
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Khrenova M. G., Nemukhin A. V., Tsirelson V. G. Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2 // Mendeleev Communications. 2020. Vol. 30. No. 5. pp. 583-585.
GOST all authors (up to 50) Copy
Khrenova M. G., Nemukhin A. V., Tsirelson V. G. Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2 // Mendeleev Communications. 2020. Vol. 30. No. 5. pp. 583-585.
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TY - JOUR
DO - 10.1016/j.mencom.2020.09.010
UR - https://mendcomm.colab.ws/publications/10.1016/j.mencom.2020.09.010
TI - Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2
T2 - Mendeleev Communications
AU - Khrenova, Mariya Grigor'evna
AU - Nemukhin, Alexander Vladimirovich
AU - Tsirelson, Vladinir Grigor'evich
PY - 2020
DA - 2020/08/31
PB - Mendeleev Communications
SP - 583-585
IS - 5
VL - 30
ER -
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@article{2020_Khrenova,
author = {Mariya Grigor'evna Khrenova and Alexander Vladimirovich Nemukhin and Vladinir Grigor'evich Tsirelson},
title = {Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2},
journal = {Mendeleev Communications},
year = {2020},
volume = {30},
publisher = {Mendeleev Communications},
month = {Aug},
url = {https://mendcomm.colab.ws/publications/10.1016/j.mencom.2020.09.010},
number = {5},
pages = {583--585},
doi = {10.1016/j.mencom.2020.09.010}
}
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Khrenova, Mariya Grigor'evna, et al. “Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2.” Mendeleev Communications, vol. 30, no. 5, Aug. 2020, pp. 583-585. https://mendcomm.colab.ws/publications/10.1016/j.mencom.2020.09.010.

Keywords

Laplacian of electron density
matrix metalloproteinase-2
metalloenzymes
nucleophilic addition
QM/MM
reactivity

Abstract

The results of quantum mechanics/molecular mechanics calculations of electron density changes upon oligopeptide hydrolysis by the matrix metalloproteinase-2 are utilized to discriminate between reactive and non-reactive enzyme–substrate complexes. Electron density depletion regions on the carbonyl carbon atom attacked by a catalytic water molecule are found on the 2D maps of electron density Laplacian in the reactive complexes. Also, the computed Fukui function quantitatively describes reactivity of the nucleophilic and electrophilic sites.

References

2.
10.1016/j.mencom.2020.09.010_bib0010
Handbook of Proteolytic Enzymes, 2013
4.
Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling
Vasilevskaya T., Khrenova M.G., Nemukhin A.V., Thiel W.
Journal of Computational Chemistry, 2015
6.
Methodological aspects of QM/MM calculations: A case study on matrix metalloproteinase-2
Vasilevskaya T., Khrenova M.G., Nemukhin A.V., Thiel W.
Journal of Computational Chemistry, 2016
7.
Theoretical study of the temperature dependence of dynamic effects in thymidylate synthase
Kanaan N., Roca M., Tuñón I., Martí S., Moliner V.
Physical Chemistry Chemical Physics, 2010
8.
Theoretical insights in enzyme catalysis
Martí S., Roca M., Andrés J., Moliner V., Silla E., Tuñón I., Bertrán J.
Chemical Society Reviews, 2004
9.
Proof of concept for poor inhibitor binding and efficient formation of covalent adducts of KRASG12C and ARS compounds
Khrenova M.G., Kulakova A.M., Nemukhin A.V.
Organic and Biomolecular Chemistry, 2020
10.
Nucleophilic addition to activated double bonds: predictions of reactivity from the Laplacian of the charge density
Carroll M.T., Cheeseman J.R., Osman R., Weinstein H.
The Journal of Physical Chemistry, 1989
12.
The experimental and theoretical QTAIMC study of the atomic and molecular interactions in dinitrogen tetroxide
Tsirelson V.G., Shishkina A.V., Stash A.I., Parsons S.
Acta Crystallographica Section B Structural Science, 2009
16.
Density functional approach to the frontier-electron theory of chemical reactivity
Parr R.G., Yang W.
Journal of the American Chemical Society, 1984
17.
A. A. Granovsky, Fairfly, http://classic.chem.msu.su/gran/firefly/index.html.
18.
General atomic and molecular electronic structure system
Schmidt M.W., Baldridge K.K., Boatz J.A., Elbert S.T., Gordon M.S., Jensen J.H., Koseki S., Matsunaga N., Nguyen K.A., Su S., Windus T.L., Dupuis M., Montgomery J.A.
Journal of Computational Chemistry, 1993
19.
Multiwfn: A multifunctional wavefunction analyzer
Lu T., Chen F.
Journal of Computational Chemistry, 2011
20.
VMD: Visual molecular dynamics
Humphrey W., Dalke A., Schulten K.
Journal of Molecular Graphics, 1996