Complex Formation between Mur Enzymes from Streptococcus pneumoniae

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: BIOCHEMISTRY; v. 58, n. 30, p. 3314-3324, JUL 30 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/12436-9 - ANTIBIO-BAC: exploring the bacterial cell wall as a target for novel antibiotherapies
• Grantee: Andrea Dessen de Souza e Silva
• Support Opportunities: Research Projects - SPEC Program
• FAPESP's process: 11/52067-6 - Assembly and structure of macromolecular complexes involved in bacterial cell wall: biosynthesis and virulence
• Grantee: Andrea Dessen de Souza e Silva
• Support Opportunities: Research Projects - SPEC Program
• FAPESP's process: 13/02451-0 - Structural characterization of an essential protein complex in cell wall formation
• Grantee: Mayara Mayele Miyachiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)