Complex Formation between Mur Enzymes from Streptococcus pneumoniae

Autor(es)

Miyachiro, Mayara M. ^{[1, 2]} ; Granato, Daniela ^[1] ; Trindade, Daniel Maragno ^[1] ; Ebel, Christine ^[2] ; Paes Leme, Adriana Franco ^[1] ; Dessen, Andrea ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13084971 Campinas, SP - Brazil

^[2] Univ Grenoble Alpes, CEA, CNRS, Inst Biol Struct, F-38000 Grenoble - France

• Tipo de documento: Artigo Científico
• Fonte: BIOCHEMISTRY; v. 58, n. 30, p. 3314-3324, JUL 30 2019.
• Citações Web of Science: 0

Resumo

Peptidoglycan is one of the major components of the bacterial cell wall, being responsible for shape and stability. Due to its essential nature, its biosynthetic pathway is the target for major antibiotics, and proteins involved in its biosynthesis continue to be targeted for inhibitor studies. The biosynthesis of its major building block, Lipid II, is initiated in the bacterial cytoplasm with the sequential reactions catalyzed by Mur enzymes, which have been suggested to form a multiprotein complex to facilitate shuttling of the building blocks toward the inner membrane. In this work, we purified MurC, MurD, MurE, MurF, and MurG from the human pathogen Streptococcus pneumoniae and characterized their interactions using chemical cross-linking, mass spectrometry, analytical ultracentrifugation, and microscale thermophoresis. Mur ligases interact strongly as binary complexes, with interaction regions mapping mostly to loop regions. Interestingly, MurC, MurD, and MurE display 10-fold higher affinity for each other than for MurF and MurG, suggesting that Mur ligases that catalyze the initial reactions in the peptidoglycan biosynthesis pathway could form a subcomplex that could be important to facilitate Lipid II biosynthesis. The interface between Mur proteins could represent a yet unexplored target for new inhibitor studies that could lead to the development of novel antimicrobials. (AU)

• Processo FAPESP: 17/12436-9 - ANTIBIO-BAC: a parede bacteriana como alvo para o desenvolvimento de novos agentes antimicrobianos
• Beneficiário: Andrea Dessen de Souza e Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa SPEC
• Processo FAPESP: 11/52067-6 - Estruturação de complexos macromoleculares da parede bacteriana: biossíntese e virulência
• Beneficiário: Andrea Dessen de Souza e Silva
• Modalidade de apoio: Auxílio à Pesquisa - Programa SPEC
• Processo FAPESP: 13/02451-0 - Caracterização estrutural de componentes de um complexo essencial para a formação da parede bacteriana
• Beneficiário: Mayara Mayele Miyachiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto