Structural characterization of an essential protein complex in cell wall formation

• Grant number: 13/02451-0
• Support type: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2013
• Effective date (End): July 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal researcher: Andrea Dessen de Souza e Silva
• Grantee: Mayara Mayele Miyachiro
• Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovações (Brasil). Campinas , SP, Brazil
• Associated research grant: 11/52067-6 - Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence, AP.SPEC
• Associated scholarship(s): 14/00570-4 - Structural characterization of an essential protein complex for bacterial cell wall formation, BE.EP.DD

Abstract

The biosynthesis of bacterial cell wall has been studied for several decades to identify targets for the development of antibiotics. However, the emergence of multidrug-resistant bacterial leads to the need to investigate and characterize new molecular targets. The synthesis of peptidoglycan, a major component of the bacterial cell wall, involves the participation of macromolecular complexes that may include cytoplasmic proteins, periplasmic and membrane. The goal of this project is carrying out the structural characterization of soluble periplasmic complex PBP2: MreC and membrane protein MraY transferase because they are essential components for the synthesis of peptidoglycan. The techniques that will be used include the expression and purification of recombinant proteins soluble and membrane, crystallization, and resolution synchrotron analysis of protein structures. The research group led by Andréa Dessen is present in two locations: at the National Laboratory of Biosciences (LNBio) in Campinas-Brazil (4 members), and at the Institut the Biologie structurale in Grenoble-France (10 members). The Thematic Project intitled "Structuring macromolecular complexes bacterial wall" will be done in Campinas, where the student Mayara Mayele Miyachiro will develop most of her thesis work. However, because the expertise of the Grenoble´s group in production and purification of membrane proteins, it would be remarkable opportunity to the student to spend some time in Grenoble to learn crucial techniques to structurally characterize the membrane protein MraY, one of the objectives of this project. The results achieved will contribute to identify novel macromolecular targets which may be used for the development of more efficient antibacterial agents. (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)

MIYACHIRO, MAYARA M.; GRANATO, DANIELA; TRINDADE, DANIEL MARAGNO; EBEL, CHRISTINE; PAES LEME, ADRIANA FRANCO; DESSEN, ANDREA. Complex Formation between Mur Enzymes from Streptococcus pneumoniae. BIOCHEMISTRY, v. 58, n. 30, p. 3314-3324, JUL 30 2019. Web of Science Citations: 0.

LADDOMADA, FEDERICA; MIYACHIRO, MAYARA M.; JESSOP, MATTHEW; PATIN, DELPHINE; JOB, VIVIANA; MENGIN-LECREULX, DOMINIQUE; LE ROY, ALINE; EBEL, CHRISTINE; BREYTON, CECILE; GUTSCHE, IRINA; DESSEN, ANDREA. The MurG glycosyltransferase provides an oligomeric scaffold for the cytoplasmic steps of peptidoglycan biosynthesis in the human pathogen Bordetella pertussis. SCIENTIFIC REPORTS, v. 9, MAR 15 2019. Web of Science Citations: 1.

LADDOMADA, FEDERICA; MIYACHIRO, MAYARA M.; DESSEN, ANDREA. Structural Insights into Protein-Protein Interactions Involved in Bacterial Cell Wall Biogenesis. ANTIBIOTICS-BASEL, v. 5, n. 2 JUN 2016. Web of Science Citations: 10.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

. Biophysical characterization of an essential protein complex for bacterial cell wall formation. 2018. 153 f. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.