Structural Modeling of Drosophila melanogaster Gut Cytochrome P450s and Docking Comparison of Fruit Fly Gut and Human Cytochrome P450s

Curr Drug Metab. 2022 May 11. doi: 10.2174/1389200223666220511162234. Online ahead of print.ABSTRACTDrosophila melanogaster is a prominent model organism in developmental biology research and in studies related to pathophysiological conditions like cancer and Alzheimer's disease. The fruit fly gut contains several cytochrome P450s (CYP450s) which have central roles in Drosophila development and in the normal physiology of the gut. Since the crystal structures of these proteins have not been deciphered yet, we modeled the structure of 29 different D. melanogaster gut CYP450s using Prime (Schrödinger). The sequences of chosen D. melanogaster gut CYP450s were compared with that of their human counterparts. The common gut (and liver) microsomal CYP450s in humans were chosen for structural comparison to find the homology and identity % of D. melanogaster CYPs with that of their human counterparts. The modeled structures were validated using PROCHECK and the best fit models were used for docking several known human pharmacological agents/drugs to the modeled D. melanogaster gut CYP450s. Based on the binding affinities (ΔG values) of the selected drug molecules with the modeled fly gut CYPs, the plausible differences in metabolism of the prominent drugs in humans and fly were projected. The gut is involved in absorption of oral drugs/pharmacological agents and hence, upregulation of intestinal CYP450 and their reactions with endobiotics and xenobiotics is envisaged. The insights g...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Source Type: research