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Architecture of the MurE-MurF ligase bacterial cell wall biosynthesis complexArchitecture of the MurE-MurF ligase bacterial cell wall biosynthesis complex
Structural highlights
FunctionA0A0T7CQ89_BORP1 Catalyzes the addition of meso-diaminopimelic acid to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanyl-D-glutamate (UMAG) in the biosynthesis of bacterial cell-wall peptidoglycan.[HAMAP-Rule:MF_00208] Involved in cell wall formation. Catalyzes the final step in the synthesis of UDP-N-acetylmuramoyl-pentapeptide, the precursor of murein.[HAMAP-Rule:MF_02019][RuleBase:RU004136] Publication Abstract from PubMedPeptidoglycan (PG) is a central component of the bacterial cell wall, and the disruption of its biosynthetic pathway has been a successful antibacterial strategy for decades. PG biosynthesis is initiated in the cytoplasm through sequential reactions catalyzed by Mur enzymes that have been suggested to associate into a multimembered complex. This idea is supported by the observation that in many eubacteria, mur genes are present in a single operon within the well conserved dcw cluster, and in some cases, pairs of mur genes are fused to encode a single, chimeric polypeptide. We performed a vast genomic analysis using >140 bacterial genomes and mapped Mur chimeras in numerous phyla, with Proteobacteria carrying the highest number. MurE-MurF, the most prevalent chimera, exists in forms that are either directly associated or separated by a linker. The crystal structure of the MurE-MurF chimera from Bordetella pertussis reveals a head-to-tail, elongated architecture supported by an interconnecting hydrophobic patch that stabilizes the positions of the two proteins. Fluorescence polarization assays reveal that MurE-MurF interacts with other Mur ligases via its central domains with K(D)s in the high nanomolar range, backing the existence of a Mur complex in the cytoplasm. These data support the idea of stronger evolutionary constraints on gene order when encoded proteins are intended for association, establish a link between Mur ligase interaction, complex assembly and genome evolution, and shed light on regulatory mechanisms of protein expression and stability in pathways of critical importance for bacterial survival. Architecture and genomic arrangement of the MurE-MurF bacterial cell wall biosynthesis complex.,Shirakawa KT, Sala FA, Miyachiro MM, Job V, Trindade DM, Dessen A Proc Natl Acad Sci U S A. 2023 May 23;120(21):e2219540120. doi: , 10.1073/pnas.2219540120. Epub 2023 May 15. PMID:37186837[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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