బయోఎనర్జెటిక్స్: ఓపెన్ యాక్సెస్

నైరూప్య

Computational Insights into the Competitive Inhibition of Acetyl Coenzyme A and Succinyl Coenzyme A of the First Step of Citric Acid Cycle

Salam Pradeep Singh and Bolin Kumar Konwar

Citric acid cycle comprises a various chemical reactions and it is required by all aerobic organisms to generate ATP. The present investigation focuses on the competitive inhibition of citrate synthase- the first step of the citric acid cycle. The known natural substrate of citrate synthase is acetyl Coenzyme A. Initially, the first substrate oxaloacetate binds to the citrate synthase which then induces the enzyme to change its conformation thus creating a binding site for the acetyl Coenzyme A. There are also several reports of citrate synthase enzyme inhibited by succinyl Coenzyme A which resembles acetyl Coenzyme A and acts as a competitive inhibitor. Hence, the present investigation deals with the molecular docking simulation studies of the two substrates viz. acetyl Coenzyme A and succinyl Coenzyme A at the active site of the citrate synthase to understand the insights into the competitive inhibition of these two substrates. Lastly, we have also
performed the density functional theory (DFT) analysis of acetyl Coenzyme A and succinyl Coenzyme A to understand the atomic charge that might contribute in the competitive inhibition. The molecular docking scores and interaction energy revealed acetyl Coenzyme A showing competitive inhibition with succinyl Coenzyme A with favourable energy. Also the DFT studies revealed the plausible caused of the competitive
inhibition at the atomic level.