4ADO

Fusidic acid resistance protein FusB

4ADO の概要

• エントリーDOI: 10.2210/pdb4ado/pdb
• 関連するPDBエントリー: 4ADN
• 分子名称: FAR1, ZINC ION (3 entities in total)
• 機能のキーワード: antibiotic resistance, protein binding protein
• 由来する生物種: STAPHYLOCOCCUS AUREUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52757.49

構造登録者

Guo, X.,Peisker, K.,Backbro, K.,Chen, Y.,Kiran, R.K.,Sanyal, S.,Selmer, M. (登録日: 2011-12-31, 公開日: 2012-03-07, 最終更新日: 2024-05-08)

主引用文献

Guo, X.,Peisker, K.,Backbro, K.,Chen, Y.,Kiran, R.K.,Mandava, C.S.,Sanyal, S.,Selmer, M.
Structure and Function of Fusb: An Elongation Factor G-Binding Fusidic Acid Resistance Protein Active in Ribosomal Translocation and Recycling
Open Biol., 2:20016-, 2012

PubMed Abstract: Fusidic acid (FA) is a bacteriostatic antibiotic that locks elongation factor G (EF-G) to the ribosome after GTP hydrolysis during elongation and ribosome recycling. The plasmid pUB101-encoded protein FusB causes FA resistance in clinical isolates of Staphylococcus aureus through an interaction with EF-G. Here, we report 1.6 and 2.3 Å crystal structures of FusB. We show that FusB is a two-domain protein lacking homology to known structures, where the N-terminal domain is a four-helix bundle and the C-terminal domain has an alpha/beta fold containing a C4 treble clef zinc finger motif and two loop regions with conserved basic residues. Using hybrid constructs between S. aureus EF-G that binds to FusB and Escherichia coli EF-G that does not, we show that the sequence determinants for FusB recognition reside in domain IV and involve the C-terminal helix of S. aureus EF-G. Further, using kinetic assays in a reconstituted translation system, we demonstrate that FusB can rescue FA inhibition of tRNA translocation as well as ribosome recycling. We propose that FusB rescues S. aureus from FA inhibition by preventing formation or facilitating dissociation of the FA-locked EF-G-ribosome complex.

PubMed: 22645663
DOI: 10.1098/RSOB.120016

実験手法

X-RAY DIFFRACTION (2.3 Å)