期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2000
卷号:97
期号:16
页码:8921-8925
DOI:10.1073/pnas.150116497
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:D-alanine-D-lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-A resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for D-alanyl-D-lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over D-alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of D-alanyl-D-lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.