Enoylpyruvate transferase

Function

Enoylpyruvate transferase (MurA) or UDP-N-acetylglucosamine 1-carboxyvinyltransferase catalyzes the ligation of phosphoenolpyruvate (PEP) to UDP-N-acetylglucosamine (UNAG). The pyruvate moiety makes the linker between the glycan and peptide portion of peptidoglycans. Thus MurA is essential for the biosynthesis of bacterial cell walls.^[1].

MurC or UDP-N-acetylmuramate-L-alanine ligase adds L-alanine in the biosynthesis of peptidoglycans which form part of the protective bacterial cell wall^[2].

Relevance

MurA is a target for antibiotics such as fosfomycin.

Structural highlights

MurA is composed of and . The active site is located at the interface of the two domains and binds the and .^[3] Water molecules are shown as red spheres.

3D Structures of enoylpyruvate transferase

Enoylpyruvate transferase 3D structures

Structure of enoylpyruvate transferase complex with fosfomycin and UDP-N-acetylglucosamine (PDB entry 3kr6)

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Brown ED, Vivas EI, Walsh CT, Kolter R. MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. PMID:7608103
↑ Humnabadkar V, Prabhakar KR, Narayan A, Sharma S, Guptha S, Manjrekar P, Chinnapattu M, Ramachandran V, Hameed SP, Ravishankar S, Chatterji M. UDP-N-acetylmuramic acid l-alanine ligase (MurC) inhibition in a tolC mutant Escherichia coli strain leads to cell death. Antimicrob Agents Chemother. 2014 Oct;58(10):6165-71. doi: 10.1128/AAC.02890-14. , Epub 2014 Aug 11. PMID:25114134 doi:http://dx.doi.org/10.1128/AAC.02890-14
↑ Skarzynski T, Mistry A, Wonacott A, Hutchinson SE, Kelly VA, Duncan K. Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. Structure. 1996 Dec 15;4(12):1465-74. PMID:8994972

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Michal Harel, Alexander Berchansky

[1] Brown ED, Vivas EI, Walsh CT, Kolter R. MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. PMID:7608103

[2] Humnabadkar V, Prabhakar KR, Narayan A, Sharma S, Guptha S, Manjrekar P, Chinnapattu M, Ramachandran V, Hameed SP, Ravishankar S, Chatterji M. UDP-N-acetylmuramic acid l-alanine ligase (MurC) inhibition in a tolC mutant Escherichia coli strain leads to cell death. Antimicrob Agents Chemother. 2014 Oct;58(10):6165-71. doi: 10.1128/AAC.02890-14. , Epub 2014 Aug 11. PMID:25114134 doi:http://dx.doi.org/10.1128/AAC.02890-14

[3] Skarzynski T, Mistry A, Wonacott A, Hutchinson SE, Kelly VA, Duncan K. Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin. Structure. 1996 Dec 15;4(12):1465-74. PMID:8994972

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