Banca de QUALIFICAÇÃO: ERIKA GEICIANNY DE CARVALHO MATIAS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : ERIKA GEICIANNY DE CARVALHO MATIAS
DATA : 04/04/2019
HORA: 09:00
LOCAL: Lab. de Aulas Teóricas - DBF
TÍTULO:

QUANTIC BIOCHEMICAL ANALYSIS OF THE REGULATOR TTGR AND ITS EFFECTS: A PERSPECTIVE ON THE DEVELOPMENT OF NEW DRUGS AGAINST THE MDR RESISTANCE MECHANISM

PALAVRAS-CHAVES:

MDR, efflux pumps, TtgR, effectors, quercetin, tetracycline, chloramphenicol, Molecular Modeling, DFT, MFCC

PÁGINAS: 64
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biofísica
SUBÁREA: Biofísica Molecular
RESUMO:

The problem of MDR bacterial resistance has become a routine event in current medicine, implying therapeutic failure. Efflux pumps collaborate considerably for this resistance to antibacterial agents. The MDR resistance mechanism, present in a variety of microorganisms, is controlled by transcriptional regulators. TtgR is a multidrug binding repressor of the TtgABC efflux pump, present in P. putida. It shows strong similarity to QacR, a multiple drug binding protein of S. aureus. We show here three crystallographic structures of TtgR, strain DOT-T1E, in complex with the flavonoid quercetin and with the antibiotics tetracycline and chloramphenicol. By means of crystallographic data and computational simulations it was possible to analyze the energetic interactions of these ligands at the general binding site of TtgR using the Functional Density Theory (DFT) and the Conjugated Layer Molecular Fractionation (MFCC) method. The results showed the energetic values of each amino acid residue constituting the binding site with the ligands under analysis. This evaluation occurred within a radius of up to 13.0 Å away from the drugs. The results showed that these ligands bind to the general binding site in a similar way, sharing residues of hydrophobic nature, such as: LEU93, LEU92, ILE141, VAL171 and VAL96. It was found some specific interactions with polar amino acids, such as ARG176, which became important for the TtgR-QUE and TtgR-TAC complexes and HIS70 for the TtgR-TAC and TtgR-CLM complexes. This energetic characterization provides us with information relevant to understanding MDR resistance, concomitant with new possibilities in drug planning versus this mechanism of resistance.

MEMBROS DA BANCA:
Presidente - 1352009 - UMBERTO LAINO FULCO
Interno - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Externo à Instituição - JOSÉ XAVIER DE LIMA NETO