Análise quântica das interações entre a enzima AKR1D1 com os hormônios esteroides testosterona e progesterona

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. ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES ; A enzima Δ4-3-cetoesteróide 5β-Redutase Humana (AKR1D1) é uma importante reguladora da biodisponibilidade de esteroides e do fenótipo metabólico. Sua ação está diretamente relacionada a doenças como: obesidade, diabetes mellitos tipo 2, doença hepática gordurosa não alcoólica entre outras. A compreensão do mecanismo de ação desta enzima é de grande importância para facilitar o desenvolvimento de tratamentos de forma mais rápida e eficiente destas doenças relacionadas a ela. Com o intuito de contribuir para essa ...