2008
DOI: 10.1016/j.jmb.2008.06.012
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Crystal Structures of Complexes of Bacterial dd-Peptidases with Peptidoglycan-Mimetic Ligands: The Substrate Specificity Puzzle

Abstract: The X-ray crystal structures of covalent complexes of the Actinomadura R39 DD-peptidase and Escherichia coli penicillin-binding protein (PBP) 5 with β-lactams bearing peptidoglycan-mimetic side chains have been determined. The structure of the hydrolysis product of an analogous peptide bound noncovalently to the former enzyme has also been obtained. The R39 DDpeptidase structures reveal the presence of a specific binding site for the D-α-aminopimelyl side chain, characteristic of the stem peptide of Actinomadu… Show more

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Cited by 39 publications
(91 citation statements)
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“…27,39 The crystal structures show a well-defined binding site for a D-α-aminopimelyl terminus. The important elements of the binding site are Tyr147 and Met414, which abut the hydrophobic tetramethylene chain, Asp142, which interacts strongly with the terminal ammonium ion, and Arg351 and Ser415, which interact with the ligand carboxylate.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…27,39 The crystal structures show a well-defined binding site for a D-α-aminopimelyl terminus. The important elements of the binding site are Tyr147 and Met414, which abut the hydrophobic tetramethylene chain, Asp142, which interacts strongly with the terminal ammonium ion, and Arg351 and Ser415, which interact with the ligand carboxylate.…”
Section: ■ Results and Discussionmentioning
confidence: 99%
“…43,44 This hypothesis is supported by the recently solved X-ray crystal structure of Actinomadura R39 DD-peptidase in complex with a cephalosporin bearing a peptidoglycan mimetic side chain. 45 This model shows specific interactions between the ammonium carboxylate group of meso-2,6-diaminopimelic acid and a subsite composed of Asp142, Tyr147, Arg351, and Ser415 (Actinomadura R39 numbering). SA-PBP3 has no equivalent residues, and the space between residues 424-427 and 621-623 is comparatively wide.…”
Section: Discussionmentioning
confidence: 99%
“…As a result, the greater distance between Ser110 and Lys213 might affect H-bond formation in smPBP5. This may interfere in the deacylation of peptidoglycan mimetic substrates while exerting DD-CPase activity (Sauvage et al, 2008), although the deacylation of Bocillin is not greatly affected (Table 3b). Due to the adverse changes in the organization of the key residues in smPBP5, the groove volume of the active site has been decreased by almost 200 Å 3 , which is the most likely reason for its lower ability to catalyse peptidoglycan mimetic substrates (Fig.…”
mentioning
confidence: 99%