Introduction
MraY, called also phospho-N-acetylmuramoyl-pentapeptide-transferase or UDP-MurNAc-pentapeptide phosphotransferase, is an integral membrane enzyme involved in peptidoglycan biosynthesis [1] [2].MraY is encoded by the mraY gene and belongs to a subfamily of the polyprenyl-phosphate N-acetyl hexosamine 1-phosphate transferase (PNPT) superfamily [3]. MRAY is a promising candidate for the development of new antibiotics. In fact, it is the target of five classes of natural nucleoside inhibitors with potent antibacterial activity [2] [4].
The structure presented in this page correspond to the MraY protein isolated from Aquifex aeolicus (strain VF5) in complex with carbacaprazamycin
Function
MraY is a critical enzyme in peptidoglycan biosynthesis. Peptidoglycan is an essential component of the cell wall of Gramnegative and Gram-positive bacteria [5]. The cell wall provides bacteria a structural support and protection. In particular, it allows bacteria to maintain their cell shape at different osmotic pressures [6]. Peptidoglycan is a cross-linked polymer of carbohydrates an amino acids and due to its biological relevance in Bacteria, it has been a major target for antibiotics [3] [5].
Peptidoglycan biosynthesis involves three main stages. MraY is responsible for the second stage. First, the peptidoglycan precursor UDP-Nacetylmuramoyl (MurNAc)–pentapeptide is synthesized in the cytosol. Second, this hydrophilic precursor is attached to a lipid carrier, and the complex lipid carrier-precursor is transported, through the membrane, to the periplasm. Third, the peptidoglycan precursors are polymerized to form the cell wall. MraY catalyzes the transfer of phospho-MurNAc-pentapeptide from hydrophilic substrate UDP-MurNAc-pentapeptide to the lipid carier (C55-P) in the presence of a Mg2+ cofactor. The product is the undecaprenyl-pyrophosphoryl-MurNAcpentapeptide, also known as lipid I [3] [7] [8].
Structure
3D related structures
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