title: Structural insights into species-specific features of the ribosome from the pathogen Staphylococcus aureus.
abstract: The emergence of bacterial multidrug resistance to antibiotics threatens to cause regression to the preantibiotic era. Here we present the crystal structure of the large ribosomal subunit from Staphylococcus aureus, a versatile Gram-positive aggressive pathogen, and its complexes with the known antibiotics linezolid and telithromycin, as well as with a new, highly potent pleuromutilin derivative, BC-3205. These crystal structures shed light on specific structural motifs of the S. aureus ribosome and the binding modes of the aforementioned antibiotics. Moreover, by analyzing the ribosome structure and comparing it with those of nonpathogenic bacterial models, we identified some unique internal and peripheral structural motifs that may be potential candidates for improving known antibiotics and for use in the design of selective antibiotic drugs against S. aureus.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Eyal
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Donna
authors.initials: D
authors.lastname: Matzov
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Krupkin
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Wekselman
authors.affiliation: Nabriva Therapeutics AG, 1110 Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Paukner
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Zimmerman
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Rozenberg
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bashan
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel ada.yonath@weizmann.ac.il.
authors.forename: Ada
authors.initials: A
authors.lastname: Yonath
mesh_terms: D011487:Protein Conformation; D012335:RNA, Ribosomal / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D012335:RNA, Ribosomal; D012269:Ribosomal Proteins
keywords: antibiotic resistance; potential advanced pleuoromutilin; protein biosynthesis; species specificity