Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1

Kulakova A.M., Khrenova M.G., Nemukhin A.V.
Тип документаJournal Article
Дата публикации2021-01-01
Название журналаBiomeditsinskaya Khimiya
ИздательRossiiskaya Akademiya Meditsinskikh Nauk
КвартильQ3
ISSN23106905
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine
Краткое описание

Human carboxylesterases are involved in the protective processes of detoxification during the hydrolytic metabolism of xenobiotics. Knowledge of the molecular mechanisms of substrates hydrolysis in the enzymes active site is necessary for the rational drug design. In this work, the molecular mechanism of the hydrolysis reaction of para-nitrophenyl acetate in the active site of human carboxylesterase was determined using modern methods of molecular modeling. According to the combined method of quantum mechanics/molecular mechanics calculations, the chemical reaction occurs within four elementary steps, including two steps of the acylation stage, and two steps of the deacylation stage. All elementary steps have low energy barriers, with the gradual lowering of the intermediate energies that stimulates reaction in the forward direction. The molecular docking was used to estimate the binding constants of the enzyme-substrate complex and the dissociation constant of enzyme-product complexes. The effective kinetic parameters of the enzymatic hydrolysis in the active site of carboxylesterase are determined by numerical solution of the differential kinetic equations.

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1. Kulakova A.M., Khrenova M.G., Nemukhin A.V. Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1 // Biomeditsinskaya Khimiya. 2021. Т. 67. № 3. С. 300–305.
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TY - JOUR

DO - 10.18097/pbmc20216703300

UR - http://dx.doi.org/10.18097/PBMC20216703300

TI - Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1

T2 - Biomeditsinskaya Khimiya

AU - Kulakova, A.M.

AU - Khrenova, M.G.

AU - Nemukhin, A.V.

PY - 2021

PB - Institute of Biochemistry

SP - 300-305

IS - 3

VL - 67

SN - 2310-6905

SN - 2310-6972

ER -

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@article{2021,

doi = {10.18097/pbmc20216703300},

url = {https://doi.org/10.18097%2Fpbmc20216703300},

year = 2021,

publisher = {Institute of Biochemistry},

volume = {67},

number = {3},

pages = {300--305},

author = {A.M. Kulakova and M.G. Khrenova and A.V. Nemukhin},

title = {Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1}

}

MLA
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Kulakova, A.M., M.G. Khrenova, and A.V. Nemukhin. “Molecular Mechanism of Chromogenic Substrate Hydrolysis in the Active Site of Human Carboxylesterase-1.” Biomeditsinskaya Khimiya 67.3 (2021): 300–305. Crossref. Web.