Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant. / Halfon, Yehuda; Matzov, Donna; Eyal, Zohar; Bashan, Anat; Zimmerman, Ella; Kjeldgaard, Jette; Ingmer, Hanne; Yonath, Ada.
I: Scientific Reports, Bind 9, Nr. 1, 11460, 2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Exit tunnel modulation as resistance mechanism of S. aureus erythromycin resistant mutant
AU - Halfon, Yehuda
AU - Matzov, Donna
AU - Eyal, Zohar
AU - Bashan, Anat
AU - Zimmerman, Ella
AU - Kjeldgaard, Jette
AU - Ingmer, Hanne
AU - Yonath, Ada
PY - 2019
Y1 - 2019
N2 - The clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 Å away from the drug’s binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ß hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further.
AB - The clinical use of the antibiotic erythromycin (ery) is hampered owing to the spread of resistance genes that are mostly mutating rRNA around the ery binding site at the entrance to the protein exit tunnel. Additional effective resistance mechanisms include deletion or insertion mutations in ribosomal protein uL22, which lead to alterations of the exit tunnel shape, located 16 Å away from the drug’s binding site. We determined the cryo-EM structures of the Staphylococcus aureus 70S ribosome, and its ery bound complex with a two amino acid deletion mutation in its ß hairpin loop, which grants the bacteria resistance to ery. The structures reveal that, although the binding of ery is stable, the movement of the flexible shorter uL22 loop towards the tunnel wall creates a wider path for nascent proteins, thus enabling bypass of the barrier formed by the drug. Moreover, upon drug binding, the tunnel widens further.
U2 - 10.1038/s41598-019-48019-1
DO - 10.1038/s41598-019-48019-1
M3 - Journal article
C2 - 31391518
AN - SCOPUS:85070353991
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 11460
ER -
ID: 226376411