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| | <StructureSection load='3zh3' size='340' side='right'caption='[[3zh3]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='3zh3' size='340' side='right'caption='[[3zh3]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zh3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Strp2 Strp2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZH3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zh3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_D39 Streptococcus pneumoniae D39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZH3 FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/UDP-N-acetylglucosamine_1-carboxyvinyltransferase UDP-N-acetylglucosamine 1-carboxyvinyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.7 2.5.1.7] </span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zh3 OCA], [https://pdbe.org/3zh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zh3 RCSB], [https://www.ebi.ac.uk/pdbsum/3zh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zh3 ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3zh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zh3 OCA], [https://pdbe.org/3zh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zh3 RCSB], [https://www.ebi.ac.uk/pdbsum/3zh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zh3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/Q04KK5_STRP2 Q04KK5_STRP2]] Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine (By similarity).[HAMAP-Rule:MF_00111][SAAS:SAAS005750_004_003895]
| + | [https://www.uniprot.org/uniprot/MURA1_STRP2 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]<ref>PMID:23571543</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Strp2]] | + | [[Category: Streptococcus pneumoniae D39]] |
| - | [[Category: UDP-N-acetylglucosamine 1-carboxyvinyltransferase]]
| + | [[Category: Gutierrez-Fernandez J]] |
| - | [[Category: Gutierrez-Fernandez, J]] | + | [[Category: Hermoso JA]] |
| - | [[Category: Hermoso, J A]] | + | |
| - | [[Category: Enolpyruvyl transferase]]
| + | |
| - | [[Category: Mura]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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][1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Engel H, Gutierrez-Fernandez J, Fluckiger C, Martinez-Ripoll M, Muhlemann K, Hermoso JA, Hilty M, Hathaway LJ. Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on murA1 gene. Antimicrob Agents Chemother. 2013 Apr 9. PMID:23571543 doi:10.1128/AAC.00223-13
- ↑ Engel H, Gutierrez-Fernandez J, Fluckiger C, Martinez-Ripoll M, Muhlemann K, Hermoso JA, Hilty M, Hathaway LJ. Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on murA1 gene. Antimicrob Agents Chemother. 2013 Apr 9. PMID:23571543 doi:10.1128/AAC.00223-13
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