Bacterial Structural Genomics Target Enabled by Recently Discovered Potent Fungal ACS Inhibitor
Nicholas D. DeBouver, Madison J. Bolejack, Taiwo E. Esan, Damian J. Krysan, Timothy J. Hagen, Jan Abendroth [1]
Molecular Tour
The compound ethyl-adenosyl monophosphate ester (ethyl-AMP) has been shown to effectively inhibit Acetyl CoA synthetase (ACS) enzymes and to facilitate the crystallization of fungal ACS enzymes in various contexts. In this study, the addition of ethyl-AMP to a bacterial ACS from Legionella pneumophila resulted in the determination of a co-crystal structure for a previously elusive structural genomics target. The dual functionality of ethyl-AMP in both inhibiting ACS enzymes and promoting crystallization establishes its significance as a valuable resource for advancing structural investigations of this class of proteins.
of L. pneumophila ACS. Red indicates the CTD, Orange is the NTD, Dark green is the NT-Ext domain, cyan is the hinge region, lime green is the ATP-binding loop, yellow is bound ethyl-AMP. (Jezewski et al, 2021[2])
References
- ↑ doi: https://dx.doi.org/10.1107/S2053230X23003801
- ↑ Jezewski AJ, Alden KM, Esan TE, DeBouver ND, Abendroth J, Bullen JC, Calhoun BM, Potts KT, Murante DM, Hagen TJ, Fox D, Krysan DJ. Structural Characterization of the Reaction and Substrate Specificity Mechanisms of Pathogenic Fungal Acetyl-CoA Synthetases. ACS Chem Biol. 2021 Aug 20;16(8):1587-1599. PMID:34369755 doi:10.1021/acschembio.1c00484
