Banca de DEFESA: ALINE DE OLIVEIRA BRAGA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ALINE DE OLIVEIRA BRAGA
DATE: 02/12/2021
TIME: 14:00
LOCAL: online
TITLE:

Molecular panorama of β-lactam resistance mediated by YcbB

KEY WORDS:

MFCC, DFT, INTERACTION ENERGY, YCBB, PBP5, MEROPENEM

PAGES: 65
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUBÁREA: Biofísica Molecular
SUMMARY:

Today, the world is fighting a common enemy: Antibiotic-resistant bacteria. Since the discovery of penicillin, science has been challenged by the ability of bacteria to develop resistance mechanisms capable of evading the pharmacological action, surviving, propagating and infecting. The resistance mechanism mediated by the L, D transpeptidase YcbB in Escherichia coli allows the cell wall to be synthesized even in the presence of the drug that inhibits the enzymes responsible for peptidoglycan
synthesis. The recruitment of YcbB, PBP5 and some accessory molecules allows the bacteria to survive even under cellular stress. As there is a real and urgent need to develop a better understanding of resistance mechanisms and consequently develop effective pharmacological solutions, the aim of this study is to evaluate, through computer simulation techniques, using Density Functional Theory (DFT) and of the Conjugated Cover Molecular Fractionation Method (MFCC), the energetic specificities present in the interaction between the YcbB complex, PBP5 and the carbapenem Meropenem. By obtaining the crystal structures in the PDB and using the tools inherent in the field of computer simulation, it was possible to analyze the energetic contributions present in each complex formed by these enzymes and meropenem. In total, 57 (68) amino acid fragments for YcbB-Meropenem (PBP5-Meropenem) were observed, with the majority of the most energetically relevant residues being part of the binding pocket and the fragments with higher attractive energy are located at a distance of up to 4 Å, in both complexes. The results showed that for the YcbB-Meropem complex the most relevant amino acids are SER526, TYR507, LEU431, ILE506, THR430 ARG407, TRP425, PRO428. For the PBP5-meropenem complex, residues THR243, HIS245, SER116, LYS242, GLY114, SER139 were the most important. The methods used to analyze these results are bold and efficient, and the results analyzed here can help to advance and innovate the pharmacological repertoire to treat infections caused by resistant bacteria.

BANKING MEMBERS:
Externo à Instituição - ANTONIO DE MACEDO FILHO - UESPI
Externa à Instituição - JÉSSICA DE FÁTIMA VIANNA - UERN
Interna - 1452833 - MARIA CELESTE NUNES DE MELO
Presidente - 1352009 - UMBERTO LAINO FULCO