Structural and dynamical origins of catalytic differences between OXA-143 and OXA-231

• Grant number: 17/22822-3
• Support Opportunities: Scholarships abroad - Research
• Start date: August 01, 2018
• End date: July 31, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Denize Cristina Favaro
• Grantee: Denize Cristina Favaro
• Host Investigator: Anthony Mittermaier
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: McGill University, Montreal, Canada

Abstract

²-lactams have been the drug of choice for the treatment of bacterial infection for many decades. However, due in part to the misuse of these antimicrobial agents, drug-resistant bacteria are posing a growing threat to global health. According to the WHO, 9 of the 12 most dangerous families of bacteria are resistant to ²-lactam antibiotics, due to the presence of ²-lactamase enzymes. Preliminary results involving ²-lactamases of the subclass oxacilinase (OXAs) suggest that both enzyme structure and internal dynamics are essential for its antibiotic resistance activity. The main goal of the present project is to elucidate the role of conformational dynamics in OXA-CHDL function and understand how they arose during evolution. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREITAS, FREDERICO CAMPOS; BORGES FERREIRA, PAULO HENRIQUE; FAVARO, DENIZE CRISTINA; DE OLIVEIRA, RONALDO JUNIO. Shedding Light on the Inhibitory Mechanisms of SARS-CoV-1/CoV-2 Spike Proteins by ACE2-Designed Peptides. JOURNAL OF CHEMICAL INFORMATION AND MODELING, v. 61, n. 3, p. 1226-1243, MAR 22 2021. (17/26131-5, 17/22822-3)

ANTUNES, VICTOR U.; LLONTOP, EDGAR E.; VASCONCELOS, FERNANDA N. DA COSTA; DE LOS SANTOS, YOSSEF LOPEZ; OLIVEIRA, RONALDO J.; LINCOPAN, NILTON; FARAH, CHUCK S.; DOUCET, NICOLAS; MITTERMAIER, ANTHONY; FAVARO, DENIZE C.. Importance of the beta 5-beta 6 Loop for the Structure, Catalytic Efficiency, and Stability of Carbapenem-Hydrolyzing Class D beta-Lactamase Subfamily OXA-143. BIOCHEMISTRY, v. 58, n. 34, p. 3604-3616, AUG 27 2019. (17/17303-7, 17/22822-3)