2ALM

Crystal structure analysis of a mutant beta-ketoacyl-[acyl carrier protein] synthase II from Streptococcus pneumoniae

Summary for 2ALM

• Entry DOI: 10.2210/pdb2alm/pdb
• Related: 1OX0
• Descriptor: 3-oxoacyl-(acyl-carrier-protein) synthase II, MAGNESIUM ION (3 entities in total)
• Functional Keywords: beta-ketoacyl-acp synthase ii, thiolase, transferase
• Biological source: Streptococcus pneumoniae
• Total number of polymer chains: 1
• Total formula weight: 46145.32

Authors

Zhang, Y.M.,Hurlbert, J.,White, S.W.,Rock, C.O. (deposition date: 2005-08-07, release date: 2005-08-30, Last modification date: 2023-08-23)

Primary citation

Zhang, Y.M.,Hurlbert, J.,White, S.W.,Rock, C.O.
Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae.
J.Biol.Chem., 281:17390-17399, 2006

PubMed Abstract: beta-Ketoacyl-ACP synthases catalyze the condensation steps in fatty acid and polyketide synthesis and are targets for the development of novel antibiotics and anti-obesity and anti-cancer agents. The roles of the active site residues in Streptococcus pneumoniae FabF (beta-ketoacyl-ACP synthase II; SpFabF) were investigated to clarify the mechanism for this enzyme superfamily. The nucleophilic cysteine of the active site triad was required for acyl-enzyme formation and the overall condensation activity. The two active site histidines in the elongation condensing enzyme have different electronic states and functions. His337 is essential for condensation activity, and its protonated Nepsilon stabilizes the negative charge developed on the malonyl thioester carbonyl in the transition state. The Nepsilon of His303 accelerated catalysis by deprotonating a structured active site water for nucleophilic attack on the C3 of malonate, releasing bicarbonate. Lys332 controls the electronic state of His303 and also plays a critical role in the positioning of His337. Phe396 functions as a gatekeeper that controls the order of substrate addition. These data assign specific roles for each active site residue and lead to a revised general mechanism for this important class of enzymes.

PubMed: 16618705
DOI: 10.1074/jbc.M513199200

Experimental method

X-RAY DIFFRACTION (2.6 Å)