2HW2

Crystal structure of Rifampin ADP-ribosyl transferase in complex with Rifampin

2HW2 の概要

• エントリーDOI: 10.2210/pdb2hw2/pdb
• 分子名称: Rifampin ADP-ribosyl transferase, GLYCINE, RIFAMPICIN, ... (4 entities in total)
• 機能のキーワード: protein-antibiotic complex, adp-ribosylation, transferase, rifampin
• 由来する生物種: Mycobacterium smegmatis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16848.99

構造登録者

Baysarowich, J.,Wright, G.D.,Junop, M. (登録日: 2006-07-31, 公開日: 2007-07-31, 最終更新日: 2024-02-14)

主引用文献

Baysarowich, J.,Koteva, K.,Hughes, D.W.,Ejim, L.,Griffiths, E.,Zhang, K.,Junop, M.,Wright, G.D.
Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr.
Proc.Natl.Acad.Sci.Usa, 105:4886-4891, 2008

PubMed Abstract: The rifamycin antibiotic rifampin is important for the treatment of tuberculosis and infections caused by multidrug-resistant Staphylococcus aureus. Recent iterations of the rifampin core structure have resulted in new drugs and drug candidates for the treatment of a much broader range of infectious diseases. This expanded use of rifamycin antibiotics has the potential to select for increased resistance. One poorly characterized mechanism of resistance is through Arr enzymes that catalyze ADP-ribosylation of rifamycins. We find that genes encoding predicted Arr enzymes are widely distributed in the genomes of pathogenic and nonpathogenic bacteria. Biochemical analysis of three representative Arr enzymes from environmental and pathogenic bacterial sources shows that these have equally efficient drug resistance capacity in vitro and in vivo. The 3D structure of one of these orthologues from Mycobacterium smegmatis was determined and reveals structural homology with ADP-ribosyltransferases important in eukaryotic biology, including poly(ADP-ribose) polymerases (PARPs) and bacterial toxins, despite no significant amino acid sequence homology with these proteins. This work highlights the extent of the rifamycin resistome in microbial genera with the potential to negatively impact the expanded use of this class of antibiotic.

PubMed: 18349144
DOI: 10.1073/pnas.0711939105

実験手法

X-RAY DIFFRACTION (1.45 Å)