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| | <StructureSection load='1rp5' size='340' side='right'caption='[[1rp5]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='1rp5' size='340' side='right'caption='[[1rp5]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1rp5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RP5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1RP5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1rp5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RP5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RP5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pyy|1pyy]], [[1k25|1k25]], [[1qme|1qme]], [[1qmf|1qmf]], [[1pmd|1pmd]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PBP2X ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1313 "Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886])</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=1rp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rp5 OCA], [https://pdbe.org/1rp5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rp5 RCSB], [https://www.ebi.ac.uk/pdbsum/1rp5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rp5 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1rp5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rp5 OCA], [http://pdbe.org/1rp5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rp5 RCSB], [http://www.ebi.ac.uk/pdbsum/1rp5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rp5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PBPX_STRPN PBPX_STRPN]] Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins. | + | [https://www.uniprot.org/uniprot/PBPX_STRPN PBPX_STRPN] Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chesnel, L]] | + | [[Category: Streptococcus pneumoniae]] |
| - | [[Category: Croize, J]] | + | [[Category: Chesnel L]] |
| - | [[Category: Dessen, A]] | + | [[Category: Croize J]] |
| - | [[Category: Dideberg, O]] | + | [[Category: Dessen A]] |
| - | [[Category: Legouellec, A]] | + | [[Category: Dideberg O]] |
| - | [[Category: Pernot, L]] | + | [[Category: Legouellec A]] |
| - | [[Category: Vernet, T]] | + | [[Category: Pernot L]] |
| - | [[Category: Antibiotic resistance]]
| + | [[Category: Vernet T]] |
| - | [[Category: Cell wall]]
| + | |
| - | [[Category: Penicillin-binding protein]]
| + | |
| - | [[Category: Peptidoglycan synthesis]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Transpeptidase]]
| + | |
| Structural highlights
Function
PBPX_STRPN Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The human pathogen Streptococcus pneumoniae is one of the main causative agents of respiratory tract infections. At present, clinical isolates of S. pneumoniae often exhibit decreased susceptibility toward beta-lactams, a phenomenon linked to multiple mutations within the penicillin-binding proteins (PBPs). PBP2x, one of the six PBPs of S. pneumoniae, is the first target to be modified under antibiotic pressure. By comparing 89 S. pneumoniae PBP2x sequences from clinical and public data bases, we have identified one major group of sequences from drug-sensitive strains as well as two distinct groups from drug-resistant strains. The first group includes proteins that display high similarity to PBP2x from the well characterized resistant strain Sp328. The second group includes sequences in which a signature mutation, Q552E, is found adjacent to the third catalytic motif. In this work, a PBP2x from a representative strain from the latter group (S. pneumoniae 5259) was biochemically and structurally characterized. Phenotypical analyses of transformed pneumococci show that the Q552E substitution is responsible for most of the reduction of strain susceptibility toward beta-lactams. The crystal structure of 5259-PBP2x reveals a change in polarity and charge distribution around the active site cavity, as well as rearrangement of strand beta3, emulating structural changes observed for other PBPs that confer drug resistance to Gram-positive pathogens. Interestingly, the active site of 5259-PBP2x is in closed conformation, whereas that of Sp328-PBP2x is open. Consequently, S. pneumoniae has evolved to employ the same protein in two distinct mechanisms of antibiotic resistance.
A PBP2x from a clinical isolate of Streptococcus pneumoniae exhibits an alternative mechanism for reduction of susceptibility to beta-lactam antibiotics.,Pernot L, Chesnel L, Le Gouellec A, Croize J, Vernet T, Dideberg O, Dessen A J Biol Chem. 2004 Apr 16;279(16):16463-70. Epub 2004 Jan 20. PMID:14734544[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pernot L, Chesnel L, Le Gouellec A, Croize J, Vernet T, Dideberg O, Dessen A. A PBP2x from a clinical isolate of Streptococcus pneumoniae exhibits an alternative mechanism for reduction of susceptibility to beta-lactam antibiotics. J Biol Chem. 2004 Apr 16;279(16):16463-70. Epub 2004 Jan 20. PMID:14734544 doi:10.1074/jbc.M313492200
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