8zo3
From Proteopedia
The crystal structures of MurK in complex with N-acetylglucosamine from Clostridium acetobutylicum
Structural highlights
FunctionMURK_CLOAB Catalyzes the ATP-dependent phosphorylation of both cell wall (peptidoglycan) amino sugars, N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc), at the 6-hydroxyl group. Neither the non-N-acetylated forms of the cell wall sugars, i.e., glucosamine and/or muramic acid, nor epimeric hexoses or 1,6-anhydro-MurNAc are substrates for the enzyme. May have a role in the rescue of the murein sugars GlcNAc and MurNAc released from muropeptides during cell wall turnover in C.acetobutylicum.[1] Publication Abstract from PubMedMurK is a MurNAc- and GlcNAc-specific amino sugar kinase, phosphorylates MurNAc and GlcNAc at the 6-hydroxyl group in an ATP-dependent manner, and contributes to the recovery of both amino sugars during the cell wall turnover in Clostridium acetobutylicum. Herein, we determined the crystal structures of MurK in complex with MurNAc, GlcNAc, and glucose, respectively. MurK represents the V-shaped fold, which is divided into a small N-terminal domain and a large C-terminal domain. The catalytic pocket is located within the deep cavity between the two domains of the MurK monomer. We mapped the significant enzyme-substrate interactions, identified key residues involved in the catalytic activity of MurK, and found that residues Asp(77) and Arg(78) from the beta4-alpha2-loop confer structural flexibilities to specifically accommodate GlcNAc and MurNAc, respectively. Moreover, structural comparison revealed that MurK adopts closed-active conformation induced by the N-acetyl moiety from GlcNAc/MurNAc, rather than closed-inactive conformation induced by glucose, to carry out its catalytic reaction. Taken together, our study provides structural and functional insights into the molecular mechanism of MurK for the phosphorylation of both MurNAc and GlcNAc, sugar substrate specificity, and conformational changes upon sugar substrate binding. Structural and biochemical insights into the molecular mechanism of N-acetylglucosamine/N-Acetylmuramic acid kinase MurK from Clostridium acetobutylicum.,He X, Liu C, Li X, Yang Q, Niu F, An L, Fan Y, Li Y, Zhou Z, Zhou H, Yang X, Liu X Int J Biol Macromol. 2024 Nov;280(Pt 2):135747. doi: , 10.1016/j.ijbiomac.2024.135747. Epub 2024 Sep 18. PMID:39304040[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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