Noland Brian W, Newman Janet M, Hendle Jörg, Badger John, Christopher Jon A, Tresser Jason, Buchanan Michelle D, Wright Tobi A, Rutter Marc E, Sanderson Wendy E, Müller-Dieckmann Hans Joachim, Gajiwala Ketan S, Buchanan Sean G
Structural Genomix, San Diego, CA 92121, USA.
Structure. 2002 Nov;10(11):1569-80. doi: 10.1016/s0969-2126(02)00879-1.
Lipid A modification with 4-amino-4-deoxy-L-arabinose confers on certain pathogenic bacteria, such as Salmonella, resistance to cationic antimicrobial peptides, including those derived from the innate immune system. ArnB catalysis of amino group transfer from glutamic acid to the 4"-position of a UDP-linked ketopyranose molecule to form UDP-4-amino-4-deoxy-L-arabinose represents a key step in the lipid A modification pathway. Structural and functional studies of the ArnB aminotransferase were undertaken by combining X-ray crystallography with biochemical analyses. High-resolution crystal structures were solved for two native forms and one covalently inhibited form of S. typhimurium ArnB. These structures permitted identification of key residues involved in substrate binding and catalysis, including a rarely observed nonprolyl cis peptide bond in the active site.
用4-氨基-4-脱氧-L-阿拉伯糖修饰脂质A可使某些病原菌（如沙门氏菌）对阳离子抗菌肽产生抗性，这些抗菌肽包括来自先天免疫系统的抗菌肽。ArnB催化将谷氨酸的氨基转移至UDP连接的酮吡喃糖分子的4''位，以形成UDP-4-氨基-4-脱氧-L-阿拉伯糖，这是脂质A修饰途径中的关键步骤。结合X射线晶体学和生化分析，对ArnB氨基转移酶进行了结构和功能研究。解析出了鼠伤寒沙门氏菌ArnB的两种天然形式和一种共价抑制形式的高分辨率晶体结构。这些结构使得能够鉴定参与底物结合和催化的关键残基，包括活性位点中一个罕见的非脯氨酰顺式肽键。
