5HL7

The crystal structure of the large ribosomal subunit of Staphylococcus aureus in complex with lefamulin

Summary for 5HL7

• Entry DOI: 10.2210/pdb5hl7/pdb
• Related: 4WCE 4WF9 4WFA 4WFB
• Descriptor: 50S ribosomal protein L2, 50S ribosomal protein L15, 50S ribosomal protein L16, ... (35 entities in total)
• Functional Keywords: ribosome, lefamulin, rna, antibiotic
• Biological source: Staphylococcus aureus subsp. aureus NCTC 8325; More
• Total number of polymer chains: 28
• Total formula weight: 1365458.03

Authors

Eyal, Z.,Matzov, D.,Krupkin, M.,Rozenberg, H.,Zimmerman, E.,Bashan, A.,Yonath, A. (deposition date: 2016-01-14, release date: 2016-12-21, Last modification date: 2024-11-20)

Primary citation

Eyal, Z.,Matzov, D.,Krupkin, M.,Paukner, S.,Riedl, R.,Rozenberg, H.,Zimmerman, E.,Bashan, A.,Yonath, A.
A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism.
Sci Rep, 6:39004-39004, 2016

PubMed Abstract: The increasing appearance of pathogenic bacteria with antibiotic resistance is a global threat. Consequently, clinically available potent antibiotics that are active against multidrug resistant pathogens are becoming exceedingly scarce. Ribosomes are a main target for antibiotics, and hence are an objective for novel drug development. Lefamulin, a semi-synthetic pleuromutilin compound highly active against multi-resistant pathogens, is a promising antibiotic currently in phase III trials for the treatment of community-acquired bacterial pneumonia in adults. The crystal structure of the Staphylococcus aureus large ribosomal subunit in complex with lefamulin reveals its protein synthesis inhibition mechanism and the rationale for its potency. In addition, analysis of the bacterial and eukaryotes ribosome structures around the pleuromutilin binding pocket has elucidated the key for the drug's selectivity.

PubMed: 27958389
DOI: 10.1038/srep39004

Experimental method

X-RAY DIFFRACTION (3.55 Å)