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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Complex Formation between Mur Enzymes from Streptococcus pneumoniae

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Miyachiro, Mayara M. [1, 2] ; Granato, Daniela [1] ; Trindade, Daniel Maragno [1] ; Ebel, Christine [2] ; Paes Leme, Adriana Franco [1] ; Dessen, Andrea [1, 2]
Total Authors: 6
[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
Total Affiliations: 2
Document type: Journal article
Source: BIOCHEMISTRY; v. 58, n. 30, p. 3314-3324, JUL 30 2019.
Web of Science Citations: 0

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)