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Unraveling Structural Disparities in Human and Mycobacterium Tuberculosis Type-I Fatty Acid Synthase

Kumar, A.; Rama, P.; Katkar, H. H.

2024-07-18 biophysics
10.1101/2024.07.17.603935 bioRxiv
Show abstract

Type-I Fatty acid synthase is an essential enzyme present in diverse species including humans (hFAS-I) and mycobacterium tuberculosis (MtbFAS-I), and is an attractive antibacterial drug target. A structural comparison of the two enzymes is essential in order to identify selective drug targets in MtbFAS-I. In this work, we have analyze equilibrium average structures of hFAS-I and MtbFAS-I obtained from 100 ns long molecular dynamics simulation trajectories. Our structural analysis revealed that two of the seven domains present in both hFAS-I and MtbFAS-I, viz. dehydratase (DH) and enoyl reductase (ER), are significantly dissimilar. We further compared corresponding catalytic pockets in these two domains and analyzed their physicochemical characteristics. In addition to being large in MtbFAS-I, the pockets are significantly different in their physicochemical characteristics and water content.

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