Crystal Structure of Human Lysozyme Complexed with N-Acetyl-α-D-glucosamine

Human lysozyme is a natural non-specific immune protein that participates in the immune response of infants against bacterial and viral infections. Lysozyme is a well-known hydrolase that cleaves peptidoglycan in bacterial cell walls. Several crystal structures of human lysozyme have been reported, but little is known regarding how it recognizes sugar molecules. In this study, the crystal structures of human lysozyme in its native and two N-acetyl-alpha-D-glucosamine (alpha-D-NAG)-bound forms were determined at 1.3 angstrom and 1.55/1.60 angstrom resolution, respectively. Human lysozyme formed a typical c-type lysozyme fold and the alpha-D-NAG molecule was bound to the middle of subsites C and D. The N-acetyl and glucosamine groups of alpha-D-NAG were stabilized by hydrophobic interactions (Val117, Ala126, and Trp127), hydrogen bonds (Asn64, Asn78, Ala126, and Val128), and water bridges. Conformational changes of Arg80, Tyr81, Val128, and Arg131 of human lysozyme were observed due to the interactions of alpha-D-NAG with the active-site cleft. The binding configuration of alpha-D-NAG in human lysozyme was distinct compared with that of other sugar-bound lysozymes. Findings from this structural analysis provide a better understanding of the sugar recognition of human lysozyme during the immune response to microbial pathogens.

Automated summary

This study determined the crystal structures of human lysozyme in its native and N-acetyl-alpha-D-glucosamine (alpha-D-NAG)-bound forms. The results revealed the interactions between human lysozyme and alpha-D-NAG, providing insights into the sugar recognition mechanism of human lysozyme during the immune response.