(acyl-carrier-protein) S-malonyltransferase

however, instead of the carboxylic acid typically found in catalytic triads, the main chain carbonyl of Gln 250 serves as a hydrogen bond acceptor in an interaction with His 201.

[3] The reaction sequence is carried out by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are shuttled between the enzymes.

[3] Malony-CoA:ACP Transacylase (FabD) is one such individual soluble protein and catalyzes the following reaction: The transfer of malonate to acyl-carrier-protein (ACP) converts the acyl groups into thioester forms which are characteristic of acyl intermediates in fatty acid synthesis and which are strictly required for the condensation reactions catalyzed by β-ketoacyl-ACP synthetase.

[4] Malonyl-CoA:ACP Transacylase uses a ping-pong kinetic mechanism with a bound malonyl ester as the acyl intermediate attached to a serine residue residing within a GHSLG pentapeptide.

[12] The difference in active site organization and predominance of type II FAS systems in bacteria make the enzymes of this pathway attractive targets for antibacterials.

[9] The simple structure and acidity of malonate seem to permit few approaches to synthesizing derivatives (acting as potential inhibitors) that retain the character of the molecule.

The crystal structure of (acyl-carrier-protein) S-malonyltransferase (FabD) in E.Coli [ 1 ] It is refined at 1.5A resolution to an R factor of 0.19l. The active site is shown in the form of a mesh grid.
FabD reaction occurs via a ping-pong mechanism. In this first step, malonate is transferred from malonyl-coA to Ser 92 in the active site. His201 plays a role in activating Ser92 for nucleophilic attack on the incoming thioester. The CoA-SH functional group is then released from the enzyme and followed by ACP binding
His201 activates the thiol of ACP for nucleophilic attack on the malonyl-Ser92 intermediate (generated in the previous step), promoting its transfer to the thiol of ACP [ 3 ]