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| | <StructureSection load='6g9s' size='340' side='right'caption='[[6g9s]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6g9s' size='340' side='right'caption='[[6g9s]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6g9s]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G9S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G9S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6g9s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6G9S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ET5:(3~{R},6~{S})-6-(aminomethyl)-4-(1,3-oxazol-5-yl)-3-(sulfooxyamino)-3,6-dihydro-2~{H}-pyridine-1-carboxylic+acid'>ET5</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]] 2.001Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6g9p|6g9p]], [[6g9f|6g9f]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ET5:(3~{R},6~{S})-6-(aminomethyl)-4-(1,3-oxazol-5-yl)-3-(sulfooxyamino)-3,6-dihydro-2~{H}-pyridine-1-carboxylic+acid'>ET5</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] </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=6g9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g9s OCA], [https://pdbe.org/6g9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6g9s RCSB], [https://www.ebi.ac.uk/pdbsum/6g9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6g9s ProSAT]</span></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=6g9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g9s OCA], [http://pdbe.org/6g9s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g9s RCSB], [http://www.ebi.ac.uk/pdbsum/6g9s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g9s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MRDA_ECOLI MRDA_ECOLI]] Catalyzes cross-linking of the peptidoglycan cell wall (PubMed:3009484). Responsible for the determination of the rod shape of the cell (PubMed:1103132). Is probably required for lateral peptidoglycan synthesis and maintenance of the correct diameter during lateral and centripetal growth (PubMed:12519203).<ref>PMID:1103132</ref> <ref>PMID:12519203</ref> <ref>PMID:3009484</ref> | + | [https://www.uniprot.org/uniprot/MRDA_ECOLI MRDA_ECOLI] Catalyzes cross-linking of the peptidoglycan cell wall (PubMed:3009484). Responsible for the determination of the rod shape of the cell (PubMed:1103132). Is probably required for lateral peptidoglycan synthesis and maintenance of the correct diameter during lateral and centripetal growth (PubMed:12519203).<ref>PMID:1103132</ref> <ref>PMID:12519203</ref> <ref>PMID:3009484</ref> |
| | <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 6g9s" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6g9s" 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: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
| + | [[Category: Levy N]] |
| - | [[Category: Levy, N]] | + | [[Category: Ruff M]] |
| - | [[Category: Ruff, M]] | + | |
| - | [[Category: Hydrolase-antibiotic complex]]
| + | |
| - | [[Category: Penicillin binding protein]]
| + | |
| Structural highlights
Function
MRDA_ECOLI Catalyzes cross-linking of the peptidoglycan cell wall (PubMed:3009484). Responsible for the determination of the rod shape of the cell (PubMed:1103132). Is probably required for lateral peptidoglycan synthesis and maintenance of the correct diameter during lateral and centripetal growth (PubMed:12519203).[1] [2] [3]
Publication Abstract from PubMed
Penicillin-binding proteins (PBPs) are the targets of the beta-lactams, the most successful class of antibiotics ever developed against bacterial infections. Unfortunately, the worldwide and rapid spread of large spectrum beta-lactam resistance genes such as carbapenemases is detrimental to the use of antibiotics in this class. New potent PBP inhibitors are needed, especially compounds that resist beta-lactamase hydrolysis. Here we describe the structure of the E. coli PBP2 in its Apo form and upon its reaction with 2 diazabicyclo derivatives, avibactam and CPD4, a new potent PBP2 inhibitor. Examination of these structures shows that unlike avibactam, CPD4 can perform a hydrophobic stacking on Trp370 in the active site of E. coli PBP2. This result, together with sequence analysis, homology modeling, and SAR, allows us to propose CPD4 as potential starting scaffold to develop molecules active against a broad range of bacterial species at the top of the WHO priority list.
Structural Basis for E. coli Penicillin Binding Protein (PBP) 2 Inhibition, a Platform for Drug Design.,Levy N, Bruneau JM, Le Rouzic E, Bonnard D, Le Strat F, Caravano A, Chevreuil F, Barbion J, Chasset S, Ledoussal B, Moreau F, Ruff M J Med Chem. 2019 May 9;62(9):4742-4754. doi: 10.1021/acs.jmedchem.9b00338. Epub, 2019 Apr 26. PMID:30995398[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Spratt BG. Distinct penicillin binding proteins involved in the division, elongation, and shape of Escherichia coli K12. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2999-3003. PMID:1103132
- ↑ Den Blaauwen T, Aarsman ME, Vischer NO, Nanninga N. Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol. 2003 Jan;47(2):539-47. PMID:12519203
- ↑ Ishino F, Park W, Tomioka S, Tamaki S, Takase I, Kunugita K, Matsuzawa H, Asoh S, Ohta T, Spratt BG, et al.. Peptidoglycan synthetic activities in membranes of Escherichia coli caused by overproduction of penicillin-binding protein 2 and rodA protein. J Biol Chem. 1986 May 25;261(15):7024-31. PMID:3009484
- ↑ Levy N, Bruneau JM, Le Rouzic E, Bonnard D, Le Strat F, Caravano A, Chevreuil F, Barbion J, Chasset S, Ledoussal B, Moreau F, Ruff M. Structural Basis for E. coli Penicillin Binding Protein (PBP) 2 Inhibition, a Platform for Drug Design. J Med Chem. 2019 May 9;62(9):4742-4754. doi: 10.1021/acs.jmedchem.9b00338. Epub, 2019 Apr 26. PMID:30995398 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00338
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