High-resolution structures of a siderophore-producing cyclization domain from Yersinia pestis offer a refined proposal of substrate binding

In vitro characterization of nonribosomal peptide synthetase-dependent O-(2-hydrazineylideneacetyl)serine synthesis indicates a stepwise oxidation strategy to generate the α-diazo ester moiety of azaserine

“…36,37,40,64,65 It has been proposed that structural changes are required for the Cy domain to catalyze heterocyclization aer peptide bond formation. 64,65 This feature may hinder the prediction of the mechanism for the peptide bond synthesis reaction. Nonetheless, it is generally believed that the peptide bond is synthesized through the direct condensation of alpha amine with thioester (Fig.…”

“…S15 †). 36,37,40,64,65 It has been proposed that structural changes are required for the Cy domain to catalyze heterocyclization aer peptide bond formation. 64,65 This feature may hinder the prediction of the mechanism for the peptide bond synthesis reaction.…”

Structural advances toward understanding the catalytic activity and conformational dynamics of modular nonribosomal peptide synthetases

“…145,164 For the cyclodehydration step, an aspartic acid not belonging to the conserved DXXXD motif appears to orient and deprotonate the cysteine side chain to promote cyclization. 164,165 Recent structures of larger, multidomain NRPS proteins containing cyclization domains, described below, provide views of the active site and interfaces with carrier domains.…”

“…Multiple structures of NRPS cyclization domains have been determined, including domains from the hybrid PKS/NRPS epothilone 20 and bacillamide 164 clusters, and two cyclization domains from the yersiniabactin pathway. 165,166 The structures illustrate the conventional condensation domain fold containing the N-and C-terminal lobes. 141 These structures offer insights into the catalytic mechanism for the two-step condensation and cyclodehydration reactions.…”