View source for 9ssi


==PENICILLIN-BINDING PROTEIN 1B (PBP-1B) in complex with Cefditoren - Streptococcus pneumoniae R6==
<StructureSection load='9ssi' size='340' side='right'caption='[[9ssi]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ssi]] 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=9SSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9SSI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDS:(2R)-2-[(1R)-1-{[(2Z)-2-(2-AMINO-1,3-THIAZOL-4-YL)-2-(METHOXYIMINO)ACETYL]AMINO}-2-OXOETHYL]-5-[(Z)-2-(4-METHYL-1,3-THIAZOL-5-YL)VINYL]-3,6-DIHYDRO-2H-1,3-THIAZINE-4-CARBOXYLIC+ACID'>CDS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=9ssi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ssi OCA], [https://pdbe.org/9ssi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ssi RCSB], [https://www.ebi.ac.uk/pdbsum/9ssi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ssi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O70038_STREE O70038_STREE] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Gram-positive pathogen Streptococcus pneumoniae, like the majority of bacteria, contains a peptidoglycan-based cell wall whose structure is highly dependent on the action of penicillin-binding proteins (PBPs). While the beta-lactam antibiotics have been employed as an antimicrobial strategy for nearly a century, much remains unclear about how inhibitor structure informs potency and PBP isoform selectivity. Here, we obtained high-resolution structures (&lt;2A) of S. pneumoniae PBP1b cocrystallized with 6 beta-lactams. Surprisingly, 2 structures feature a noncanonical conformation of the covalent "acyl-enzyme complex." To clarify how protein-ligand interactions mediate inhibitor binding, we applied molecular modeling and molecular mechanics-based dynamics analyses. Our analyses illustrate how seemingly minimal changes to inhibitor structure modulate beta-lactam binding mode and inhibitor potency, as described by the metric k(inact)/K(I). Furthermore, we demonstrate that persistent interaction in the covalent acyl-enzyme complex between the inhibitor carboxylate and a highly conserved three-residue motif is not fully predictive of k(inact)/K(I) for PBP1b. In silico modeling suggests that the noncovalent preacyl complex may leverage this interaction, but a postacylation change in ligand conformation may accompany acylation in some inhibitors. The elucidation of key PBP1b ligand-receptor interactions pre- and postacylation will inform the rational design of novel PBP inhibitors and probes.

Structural and Dynamics Analyses of beta-Lactam Inhibition of Streptococcus pneumoniae Penicillin-Binding Protein 1b (PBP1b) Guide Interrogation of Structure-Activity Relationships.,Flanders PL, Gillingham JR, Contreras-Martel C, Dessen A, Carlson EE, Ambrose EA ACS Chem Biol. 2026 Jan 27. doi: 10.1021/acschembio.5c00788. PMID:41589753<ref>PMID:41589753</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9ssi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae R6]]
[[Category: Ambrose EA]]
[[Category: Carlson EE]]
[[Category: Contreras-Martel C]]
[[Category: Dessen A]]
[[Category: Flanders PL]]
[[Category: Gillingham JR]]