3pbq: Difference between revisions
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==Crystal structure of PBP3 complexed with imipenem== | ==Crystal structure of PBP3 complexed with imipenem== | ||
<StructureSection load='3pbq' size='340' side='right' caption='[[3pbq]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='3pbq' size='340' side='right'caption='[[3pbq]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3pbq]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3pbq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PBQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PBQ FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IM2:(5R)-5-[(1S,2R)-1-FORMYL-2-HYDROXYPROPYL]-3-[(2-{[(E)-IMINOMETHYL]AMINO}ETHYL)SULFANYL]-4,5-DIHYDRO-1H-PYRROLE-2-CARBOXYLIC+ACID'>IM2</scene></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=3pbq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pbq OCA], [https://pdbe.org/3pbq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pbq RCSB], [https://www.ebi.ac.uk/pdbsum/3pbq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pbq ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/FTSI_PSEAE FTSI_PSEAE] Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080]<ref>PMID:20580675</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Penicillin-binding protein|Penicillin-binding protein]] | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pseudomonas aeruginosa PAO1]] | ||
[[Category: | [[Category: Han S]] | ||
Latest revision as of 13:18, 6 November 2024
Crystal structure of PBP3 complexed with imipenemCrystal structure of PBP3 complexed with imipenem
Structural highlights
FunctionFTSI_PSEAE Catalyzes cross-linking of the peptidoglycan cell wall at the division septum (By similarity). Binds penicillin (PubMed:20580675).[HAMAP-Rule:MF_02080][1] Publication Abstract from PubMedPseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes nosocomial infections for which there are limited treatment options. Penicillin-binding protein PBP3, a key therapeutic target, is an essential enzyme responsible for the final steps of peptidoglycan synthesis and is covalently inactivated by beta-lactam antibiotics. Here we disclose the first high resolution cocrystal structures of the P. aeruginosa PBP3 with both novel and marketed beta-lactams. These structures reveal a conformational rearrangement of Tyr532 and Phe533 and a ligand-induced conformational change of Tyr409 and Arg489. The well-known affinity of the monobactam aztreonam for P. aeruginosa PBP3 is due to a distinct hydrophobic aromatic wall composed of Tyr503, Tyr532, and Phe533 interacting with the gem-dimethyl group. The structure of MC-1, a new siderophore-conjugated monocarbam complexed with PBP3 provides molecular insights for lead optimization. Importantly, we have identified a novel conformation that is distinct to the high-molecular-weight class B PBP subfamily, which is identifiable by common features such as a hydrophobic aromatic wall formed by Tyr503, Tyr532, and Phe533 and the structural flexibility of Tyr409 flanked by two glycine residues. This is also the first example of a siderophore-conjugated triazolone-linked monocarbam complexed with any PBP. Energetic analysis of tightly and loosely held computed hydration sites indicates protein desolvation effects contribute significantly to PBP3 binding, and analysis of hydration site energies allows rank ordering of the second-order acylation rate constants. Taken together, these structural, biochemical, and computational studies provide a molecular basis for recognition of P. aeruginosa PBP3 and open avenues for future design of inhibitors of this class of PBPs. Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa.,Han S, Zaniewski RP, Marr ES, Lacey BM, Tomaras AP, Evdokimov A, Miller JR, Shanmugasundaram V Proc Natl Acad Sci U S A. 2010 Dec 6. PMID:21135211[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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