masterThesis
Análise quântica das interações entre a enzima AKR1D1 com os hormônios esteroides testosterona e progesterona
Fecha
2020-10-30Registro en:
SOUZA, Lucas Marques de. Análise quântica das interações entre a enzima AKR1D1 com os hormônios esteroides testosterona e progesterona. 2020. 62f. Dissertação (Mestrado em Ciências Biológicas) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2020.
Autor
Souza, Lucas Marques de
Resumen
The enzyme Δ4-3-cetosteroid 5β-Human Redutase (AKR1D1) is an essential regulator for
bioavailability of steroids and metabolic phenotype. Its activity is directly related to diseases
such as: obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, among others.
Understanding how this enzyme works is of great importance to improve speed and efficiency
in the development of disease treatments. Bearing this in mind, interactions between enzyme
AKR1D1 with the two main masculine and feminine steroid hormones, testosterone and
progesterone respectively, have been analyzed using quantum mechanics and computational
simulation techniques - the density-functional theory (DFT) and the molecular fractionation
with conjugate caps (MFCC) method. In the complex Testosterone-AKR1D1 the amino acid
residues that mostly contributed to attraction were: TRP230 > TYR26 > ASN227 > TYR132 >
SER225; in complex Progesterone-AKR1D1 they were: GLU120 > TRP230 > TYR58 >
TYR132 > ILE57. The complex with Testosterone, located in the allosteric site of the protein,
presented a higher energy of total interaction when compared to the location of progesterone in
the active site. The residue TRP230 had a prominent role in both systems, reinforcing its
important function of positioning the binder inside the enzyme. And GLU120, residue of the
catalytic tetrad, showed the highest energy of interaction of AKR1D1 with progesterone.