PDBsum entry 3zh4

Transferase

PDB id: 3zh4

Contents

Protein chain

411 a.a.

Ligands

FLC

PEG

Waters ×347

PDB id:

3zh4

Name:

Transferase

Title:

Crystal structure of s. Pneumoniae hungary 19a mura1 in complex with citrate

Structure:

Udp-n-acetylglucosamine 1-carboxyvinyltransferase. Chain: a. Synonym: enoylpyruvate transferase, udp-n-acetylglucosamine enolpyruvyl transferase. Engineered: yes

Source:

Streptococcus pneumoniae. Organism_taxid: 1313. Strain: hungary 19a-6. Atcc: 700673. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.80Å R-factor: 0.163 R-free: 0.204

Authors:

J.Gutierrez-Fernandez,J.A.Hermoso

Key ref:

H.Engel et al. (2013). Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on the murA1 gene. Antimicrob Agents Chemother, 57, 2801-2808. PubMed id: 23571543 DOI: 10.1128/AAC.00223-13

Date:

20-Dec-12 Release date: 24-Apr-13

Protein chain

B1IBM3  (MURA1_STRPI) -  UDP-N-acetylglucosamine 1-carboxyvinyltransferase from Streptococcus pneumoniae (strain Hungary19A-6)

Seq: 419 a.a.

Struc: 411 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.7 - UDP-N-acetylglucosamine 1-carboxyvinyltransferase.
• Pathway: Peptidoglycan Biosynthesis (Part 1)
• Reaction: phosphoenolpyruvate + UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-3- O-(1-carboxyvinyl)-alpha-D-glucosamine + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1128/AAC.00223-13

Antimicrob Agents Chemother 57:2801-2808 (2013)

PubMed id: 23571543

Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on the murA1 gene.

H.Engel, J.Gutiérrez-Fernández, C.Flückiger, M.Martínez-Ripoll, K.Mühlemann, J.A.Hermoso, M.Hilty, L.J.Hathaway.

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 (Ala364Thr). 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.