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Crystal structure of MraY, an essential membrane enzyme in bacterial cell wall synthesis (775.1)
Author(s) -
Lee SeokYong,
Chung Ben
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.775.1
Subject(s) - aquifex aeolicus , peptidoglycan , transferase , translocase , cell envelope , streptomyces coelicolor , lipid ii , bacterial cell structure , biochemistry , chemistry , enzyme , cell wall , biology , bacteria , mutant , gene , genetics , escherichia coli , chromosomal translocation
The Phospho‐MurNAc‐pentapeptide translocase (MraY) is a membrane‐spanning enzyme involved in an essential process of bacterial cell wall synthesis: transfer of the peptidoglycan precursor phosphor‐MurNAc‐pentapeptide to the carrier lipid undecaprenyl phosphate. MraY belongs to a subfamily of the polyprenyl‐phosphate N‐acetyl hexosamine 1‐phosphate transferase (PNPT) superfamily whose members are involved in various biological processes including prokaryotic cell envelope polymer synthesis and eukaryotic N‐linked glycosylation. MraY has been a promising target for the development of antibiotics because it is the target of many different classes of natural product antibiotics. Despite the importance, the lack of a structure has hampered our understanding of the mechanism of the enzyme function and inhibition by natural product inhibitors. We report the crystal structure of MraY from Aquifex aeolicus (MraYAA) at 3.3 Å resolution, the first structure of a member of the PNPT superfamily. The crystal structure, together with crystallographic and functional studies, reveals the architecture of MraYAA, the location of Mg2+ at the active site and the putative binding sites of both substrates. Our crystallographic studies provide insights into the mechanism of how MraY attaches a building block of peptidoglycan to a carrier lipid.