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9.B.146 The Putative Undecaprenyl-phosphate N-Acetylglucosaminyl Transferase (MurG) Family

The MurG family cosists of thousands of glycosyltransferases, many of which function in bacterial cell wall (peptidoglycan) synthesis.  This family is also designated the Glycosyl Transferase (GT) 4, GT4, family, the WecA-like family and the Rfe family.  Homologues are found in both prokaryotes and eukaryotes and vary in size from about 300 aas to over 500 aas.  They usually exhibit 10 - 15 putative TMSs. The crystal structure of one member of this family, MraY of Aquifex aeolicus, the cell wall biosynthesis enzyme, phospho-MurNAc-pentapeptide translocase, has been solved at 3.3Å resolution (Chung et al. 2013).  The structure of this 10 TMS protein reveals the Mg2+ binding site and the probable basis for catalysis.

Translocation of the peptidoglycan precursor Lipid II across the cytoplasmic membrane is a key step in bacterial cell wall synthesis. Using NBD-labelled Lipid II, van Dam et al. (2007) showed that Lipid II transport does not occur spontaneously and is not induced by the presence of single spanning helical transmembrane peptides that facilitate transbilayer movement of membrane phospholipids. MurG catalyses synthesis of Lipid II from Lipid I in lipid vesicles, but it did not result in membrane translocation of Lipid II. It was suggested that a specialized protein machinery is needed for transmembrane movement of Lipid II. It could be demonstrated that Lipid II translocation occurred in isolated Escherichia coli inner membrane vesicles and this transport could be uncoupled from the synthesis of Lipid II at low temperatures. The transport process appeared to be independent of an energy source (ATP or proton motive force).  Lipid II transport may be coupled to transglycosylation activity on the periplasmic side of the inner membrane (van Dam et al. 2007).

In Escherichia coli, many enzymes including MurG are directly involved in the synthesis and assembly of peptidoglycan. MurG is an essential glycosyltransferase catalysing the last intracellular step of peptidoglycan synthesis. MurG exhibits a random distribution in the cell envelope with a relatively high intensity at the division site. This mid-cell localization is dependent on the presence of a mature divisome (Mohammadi et al. 2007). Its localization in the lateral cell wall appears to require the presence of MreCD. This could indicate a potential interaction between MurG and other proteins. MurG also associates with MreB and MraY in the same protein complex. The loss of rod shape of a mreBCD deletion strain could be ascribed to the loss of MurG membrane localization. Consequently, this could prevent the localized supply of the lipid II precursor to the peptidoglycan synthesizing machinery involved in cell elongation. Possibly the involvement of MurG in peptidoglycan synthesis concerns two complexes, one implicated in cell elongation and the other in division.

References associated with 9.B.146 family:

Chung, B.C., J. Zhao, R.A. Gillespie, D.Y. Kwon, Z. Guan, J. Hong, P. Zhou, and S.Y. Lee. (2013). Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis. Science 341: 1012-1016. 23990562
Mohammadi, T., A. Karczmarek, M. Crouvoisier, A. Bouhss, D. Mengin-Lecreulx, and T. den Blaauwen. (2007). The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli. Mol. Microbiol. 65: 1106-1121. 17640276
van Dam, V., R. Sijbrandi, M. Kol, E. Swiezewska, B. de Kruijff, and E. Breukink. (2007). Transmembrane transport of peptidoglycan precursors across model and bacterial membranes. Mol. Microbiol. 64: 1105-1114. 17501931