6xhw

From Proteopedia

Jump to: navigation, search

Crystal structure of the A2058-unmethylated Thermus thermophilus 70S ribosome in complex with mRNA, aminoacylated A- and P-site tRNAs, and deacylated E-site tRNA at 2.50A resolution

Structural highlights

6xhw is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:0TD, 2MA, 2MG, 2MU, 31H, 4OC, 4SU, 5MC, 5MU, 7MG, F3N, K, M2G, MA6, MG, MIA, OMG, PSU, UR3, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL2_THET8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B]

Publication Abstract from PubMed

Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 A resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance.

Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance.,Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, Polikanov YS Nat Chem Biol. 2021 Apr;17(4):412-420. doi: 10.1038/s41589-020-00715-0. Epub 2021 , Jan 18. PMID:33462493[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
9 reviews cite this structure
Mechanisms of Resistance to Macrolide Antibiotics among <i>Staphylococcus aureus</i>.
Miklasińska-Majdanik et al. (2021)
8 more
37 other articles
No citations found

See Also

References

  1. ↑ Svetlov MS, Syroegin EA, Aleksandrova EV, Atkinson GC, Gregory ST, Mankin AS, Polikanov YS. Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nat Chem Biol. 2021 Apr;17(4):412-420. PMID:33462493 doi:10.1038/s41589-020-00715-0

Contents


PDB ID 6xhw

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/6xhw"
Personal tools