3zh3

crystal structure of S. pneumoniae D39 native MurA1

spinqualitylabelsall models 3zh3, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3zh3 is a 1 chain structure with sequence from Streptococcus pneumoniae D39. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MURA1_STRP2 Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine (By similarity). Target for the antibiotic fosfomycin. Involved in heteroresistance to antibiotic fosfomycin. Heteroresistance is the ability of a clonal population to grow one or several subpopulations at a frequency of 10(-7) to 10(-3) in the presence of a higher antibiotic concentration than that predicted to be effective by measurement of the minimum inhibitory concentration (MIC) (PubMed:23571543).[HAMAP-Rule:MF_00111] Publication Abstract from PubMed 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 one (Hungary19A) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary19A differs from the other strains by a single amino-acid substitution in MurA1 (Ala364Thr). To test whether this substitution is responsible for lack of heteroresistance, it was introduced into strain D39. The heteroresistant phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between MurA1 of the heteroresistant strain D39 or the non-heteroresistant strain Hungary19A were found in their crystal structures. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype in 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. Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on murA1 gene.,Engel H, Gutierrez-Fernandez J, Fluckiger C, Martinez-Ripoll M, Muhlemann K, Hermoso JA, Hilty M, Hathaway LJ Antimicrob Agents Chemother. 2013 Apr 9. PMID:23571543 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoylpyruvate transferase 3D structures

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