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| | ==Penicillin-Binding Protein 2X (PBP2X) from Streptococcus pneumoniae in complex with oxacillin== | | ==Penicillin-Binding Protein 2X (PBP2X) from Streptococcus pneumoniae in complex with oxacillin== |
| - | <StructureSection load='5oiz' size='340' side='right' caption='[[5oiz]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='5oiz' size='340' side='right'caption='[[5oiz]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oiz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Strr6 Strr6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OIZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OIZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oiz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OIZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1S6:(2R,4S)-5,5-DIMETHYL-2-[(1R)-1-{[(5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)CARBONYL]AMINO}-2-OXOETHYL]-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>1S6</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]] 2.7Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pbpX, spr0304 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=171101 STRR6])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1S6:(2R,4S)-5,5-DIMETHYL-2-[(1R)-1-{[(5-METHYL-3-PHENYL-1,2-OXAZOL-4-YL)CARBONYL]AMINO}-2-OXOETHYL]-1,3-THIAZOLIDINE-4-CARBOXYLIC+ACID'>1S6</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5oiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oiz OCA], [http://pdbe.org/5oiz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oiz RCSB], [http://www.ebi.ac.uk/pdbsum/5oiz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oiz 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=5oiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oiz OCA], [https://pdbe.org/5oiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oiz RCSB], [https://www.ebi.ac.uk/pdbsum/5oiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oiz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PBPX_STRR6 PBPX_STRR6]] 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_STRR6 PBPX_STRR6] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5oiz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5oiz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Strr6]] | + | [[Category: Large Structures]] |
| - | [[Category: Bernardo-Garcia, N]] | + | [[Category: Streptococcus pneumoniae R6]] |
| - | [[Category: Hermoso, J A]] | + | [[Category: Bernardo-Garcia N]] |
| - | [[Category: Antibiotic]]
| + | [[Category: Hermoso JA]] |
| - | [[Category: B-lactam]]
| + | |
| - | [[Category: Cell-wall]] | + | |
| - | [[Category: Penicillin]]
| + | |
| - | [[Category: Transpeptidase]]
| + | |
| Structural highlights
Function
PBPX_STRR6 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.
Publication Abstract from PubMed
Transpeptidases, members of the penicillin-binding protein (PBP) families, catalyze cross-linking of the bacterial cell wall. This transformation is critical for the survival of bacteria, and it is the target of inhibition by beta-lactam antibiotics. We report herein our structural insights into catalysis by the essential PBP2x of Streptococcus pneumoniae by disclosing a total of four X-ray structures, two computational models based on the crystal structures, and molecular-dynamics simulations. The X-ray structures are for the apo PBP2x, the enzyme modified covalently in the active site by oxacillin (a penicillin antibiotic), the enzyme modified by oxacillin in the presence of a synthetic tetrasaccharide surrogate for the cell-wall peptidoglycan, and a noncovalent complex of cefepime (a cephalosporin antibiotic) bound to the active site. A prerequisite for catalysis by transpeptidases, including PBP2x, is the molecular recognition of nascent peptidoglycan strands, which harbor pentapeptide stems. We disclose that the recognition of nascent peptidoglycan by PBP2x takes place by complexation of one pentapeptide stem at an allosteric site located in the PASTA domains of this enzyme. This binding predisposes the third pentapeptide stem in the same nascent peptidoglycan strand to penetration into the active site for the turnover events. The complexation of the two pentapeptide stems in the same peptidoglycan strand is a recognition motif for the nascent peptidoglycan, critical for the cell-wall cross-linking reaction.
Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae.,Bernardo-Garcia N, Mahasenan KV, Batuecas MT, Lee M, Hesek D, Petrackova D, Doubravova L, Branny P, Mobashery S, Hermoso JA ACS Chem Biol. 2018 Mar 16;13(3):694-702. doi: 10.1021/acschembio.7b00817. Epub, 2018 Jan 30. PMID:29357220[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bernardo-Garcia N, Mahasenan KV, Batuecas MT, Lee M, Hesek D, Petrackova D, Doubravova L, Branny P, Mobashery S, Hermoso JA. Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae. ACS Chem Biol. 2018 Mar 16;13(3):694-702. doi: 10.1021/acschembio.7b00817. Epub, 2018 Jan 30. PMID:29357220 doi:http://dx.doi.org/10.1021/acschembio.7b00817
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