Banca de DEFESA: GILMARA BARROS DE LIMA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : GILMARA BARROS DE LIMA
DATA : 07/07/2021
HORA: 09:30
LOCAL: Modo remoto - via google meet
TÍTULO:

MOLECULAR MODELING OF RBMTI-A INHIBITORY DOMAINS, AN INHIBITOR OF SERINOPROTEASES AND STUDY, IN SILICO, OF THEIR INTERACTION WITH PROTEASES INVOLVED IN THE PULMONARY INFLAMMATORY PROCESS

PÁGINAS: 110
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
SUBÁREA: Biologia Molecular
RESUMO:

Protease inhibitors are promising therapeutic agents for lung diseases. rBmTI-A is a serine protease inhibitor that, in previous studies, prevented the development of porcine pancreatic elastase-induced pulmonary emphysema in mice. The rBmTI-A inhibitor is an inhibitor belonging to the Kunitz-BPTI family, has two inhibitory domains and a molecular mass around 14 kDa. The rBmTI-A inhibitor has activity on bovine trypsin, human plasma kallikrein, human neutrophil elastase and plasmin. In this study, three-dimensional models were obtained for the inhibitory domains of rBmTI-A (D1 and D2) that were validated by a series of quality analyzes that took into account stereochemical, atomic contacts and folding parameters. These models were then used for molecular interaction studies with serine proteases HNE, KLK1, KLK, all of them involved in the context of Chronic Obstructive Pulmonary Disease (COPD) and trypsin. According to the results of binding free energy and dissociation constant, the molecular docking experiments showed the possibility of interaction between the inhibitor domains and serinoproteases, with the best results for the complex formed between HNE and rBmTI-A1 (ΔG = -10.9 kcal mol-1 and Kd at 35ºC = 1.7x 10^-8 M); for the complex formed between KLK1 and rBmTI-A2 (ΔG = -11.6 kcal.mol-1 , Kd at 35ºC = 6.1x 10^-9M); for the complex formed between KLK3 and rBmTI-A1 (ΔG = -11.5 kcal.mol-1 , Kd at 35ºC = 6,4x10^-9M) and for the complex formed between trypsin and rBmTI-A2 (ΔG = -12.5 kcal.mol-1 and Kd at 35ºC = 2.4x10^-9M). The results show that rBmTI-A is an efficient serinoprotease inhibitor, however the inhibitory domains acting independently present little difference to the effect of the complete inhibitor. The rBmTI-A1 domain shows greater interaction with KLK3 and HNE, respectively, and the rBmTI-A2 domain shows greater interaction with KLK1 and trypsin, respectively.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 2605490 - SERGIO DAISHI SASAKI
Membro Titular - Examinador(a) Interno ao Programa - 000.000.000-00 - RENATO FERREIRA DE FREITAS - UFABC
Membro Titular - Examinador(a) Externo ao Programa - 1732829 - ANA CAROLINA QUIRINO SIMOES
Membro Suplente - Examinador(a) Interno ao Programa - 1696841 - LUCIANO PUZER
Membro Suplente - Examinador(a) Externo à Instituição - ADRIANA FELICIANO ALVES DURAN - UNIMES