Structural basis for linezolid binding site rearrangement in the Staphylococcus aureus ribosome

• Main Authors: Tofayel Ahmed, Belousoff, Matthew J., Eyal, Zohar, Radjainia, Mazdak, Bamert, Rebecca S., Matzov, Donna, Bashan, Anat, Zimmerman, Ella, Mishra, Satabdi, Cameron, David, Elmlund, Hans, Peleg, Anton Y., Bhushan, Shashi, Lithgow, Trevor, Yonath, Ada
• Other Authors: Zhang, Gongyi
• Format: Article
• Language: English
• Published: 2019
• Subjects: Staphylococcus; Antibiotic Resistance; Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/87660; http://hdl.handle.net/10220/50196
• Institution: Nanyang Technological University

An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of Staphylococcus aureus. This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 Å away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site.