3ZH4

crystal structure of S. pneumoniae Hungary 19A MurA1 in complex with citrate

3ZH4 の概要

• エントリーDOI: 10.2210/pdb3zh4/pdb
• 分子名称: UDP-N-ACETYLGLUCOSAMINE 1-CARBOXYVINYLTRANSFERASE, CITRATE ANION, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: transferase, mura
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• 細胞内の位置: Cytoplasm (By similarity): B1IBM3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45397.93

構造登録者

Gutierrez-Fernandez, J.,Hermoso, J.A. (登録日: 2012-12-20, 公開日: 2013-04-24, 最終更新日: 2023-12-20)

主引用文献

Engel, H.,Gutierrez-Fernandez, J.,Fluckiger, C.,Martinez-Ripoll, M.,Muhlemann, K.,Hermoso, J.A.,Hilty, M.,Hathaway, L.J.
Heteroresistance to Fosfomycin is Predominant in Streptococcus Pneumoniae and Depends on Mura1 Gene.
Antimicrob.Agents Chemother., 57:2801-, 2013

PubMed Abstract: Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae. We found that of 11 strains tested, all but 1 (Hungary(19A)) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary(19A) differs from the other strains by a single amino acid substitution in MurA1 (Ala(364)Thr). To test whether this substitution is responsible for the lack of heteroresistance, it was introduced into strain D39. The heteroresistance phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between the MurA1 crystal structures of heteroresistant strain D39 and nonheteroresistant strain Hungary(19A) were found. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype of S. pneumoniae and that MurA1 is required for heteroresistance to fosfomycin but is not the only factor involved. The findings provide a caveat for any future use of fosfomycin in the treatment of pneumococcal infections.

PubMed: 23571543
DOI: 10.1128/AAC.00223-13

実験手法

X-RAY DIFFRACTION (1.8 Å)