Banca de QUALIFICAÇÃO: LUCAS MARQUES DE SOUZA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : LUCAS MARQUES DE SOUZA
DATE: 01/10/2020
TIME: 09:00
LOCAL: Online
TITLE:

QUANTUM ANALYSIS OF THE PARTICULARITIES THAT GOVERN THE UNPRODUCTIVE INTERACTION OF THE TESTOSTERONE-AKR1D1 COMPLEX AND THE PRODUCTIVE INTERACTION OF PROGESTERONE-AKR1D1

KEY WORDS:

AKR1D1; Steroid hormones; Testosterone; Progesterone; DFT; MFCC.

PAGES: 48
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUBÁREA: Biofísica Molecular
SUMMARY:

The Δ 4 -3-keto steroid 5beta reductase enzyme (AKR1D1) belongs to subfamily 1 of the aldo-keto reductase (AKRs) superfamily, is a first step in the metabolism of steroid hormones and is essential for the synthesis of all bile acids. Present in all phyla, AKRs are enzymes dependent on the NADP cofactor and, to date, more than 190 types have been identified, distributed in 16 subfamilies. Highly expressed in the liver, 5beta reductase has a characteristic that makes it unique among members of its family, which is the replacement of histidine in the tetracatalytic group conserved by glutamic acid 120 (Glu120). This substitution allows the saturation of the double bond between carbon C4 and C5 to produce a 90º curve between the A / B rings of the steroid resulting in a cis configuration. Recent studies increasingly demonstrate the importance of this enzyme for maintaining and healthy functioning of the human body. However, some of its functions and mechanisms still need to be outlined. The present study analyzed qualitatively and quantitatively, using quantum mechanics and computer simulation techniques, the behavior of the interactions that determine the non-productive union of testosterone with the enzyme AKR1D1 (TES-AKR1D1) and the productive union of progesterone with AKR1D1 ( PRO-AKR1D1). Of the set of 325 amino acids present in Monomer A, only 77 in the TES-AKR1D1 complex and 75 in the PRO-AKR1D1 complex showed significant energetic interactions for the systems. Because they have very different positions within the enzyme, since testosterone is positioned at the allosteric site while progesterone is positioned at the active site of the enzyme, there was a relevant difference between the amino acids that contributed most to the systems. The five most relevant of the TES-AKR1D1 complexes were: TRP230> TYR26> ASN227> TYR132> SER225; and the PRO-AKR1D1 complex were: GLU120> TRP230> TYR58> TYR132> ILE57. TRP230 showed a prominent position in both systems, reinforcing its important role of positioning the ligand within the enzyme. The analyzes present in this work can contribute to elucidate issues inherent to the productive and non-productive behavior of the enzyme and the mechanism of action of AKR1D1.

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