Beta-ketoacyl-acyl carrier protein (ACP) synthase enzymes join short carbon units to construct fatty acyl chains by a three-step Claisen condensation reaction. The reaction starts with a trans thioesterification of the acyl primer substrate from ACP to the enzyme. Subsequently, the donor substrate malonyl-ACP is decarboxylated to form a carbanion intermediate, which in the third step attacks C1 of the primer substrate giving rise to an elongated acyl chain.
The IDP00577 protein, 3-oxoacyl-(acyl carrier protein) synthase I from Yersinia pestis CO92, was co-crystallized with CoA, however, there was no ligand bound in the final Se-Met structure (PDB ID code 3OYT). Nevertheless, the catalytic Cys164 in chain A seems to be covalently modified with an unknown ligand, which was not modeled because of its noncontinuous electron density. This ligand is solvent oriented, whereas caprylic acid in the homologous 3-oxoacyl-(acyl carrier protein) synthase I structure from E.coli (PDB ID code 2BUI), which covalently bound to Cys163, is embedded into a narrow strongly hydrophobic pocket of the protein. Phe393 (in our structure) and Phe392 (2BUI) might function as a gate residue allowing the relocation of covalently bound product from the solvent side, i.e. from the substrate-binding site to the protein's core. The Phe393 in chain B has alternative side chain conformations, which shows close and open state of the aforementioned pocket. Moreover, Met139 in the 3OYT structure adopts alternative side chain conformations in response to the position of Phe393 side chain.
The stretch of residues 268 through 275 in the Y. pestis fabB structure adopts a loop conformation. The loop hides a possible area of fabB that is used by the protein’s substrate(s) for interaction. The loop is ordered in chain A and flexible in chain B, indicating that the mobility of this secondary structure element might be a requirement for the productive complex formation between fabB and its substrate(s). The C-alpha atom of Val271 in the loop is 4.8 A from the C-alpha atom of aforementioned Phe393.