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Recent studies have identified the role of TMAO, a metabolite produced by gut microbial choline metabolism in increasing the risk for major adverse cardiovascular events. The bacterial enzyme Choline TMA Lyase found in several opportunistic gut commensals produces TMA, a precursor of TMAO. Proteus bacteria, a key contributor in several gastrointestinal diseases, is known to survive in the wide pH range of 2-10, offered by different locations of the GI tract. Currently, evidence characterising the functionality of the protein in the different compartments of the gut is lacking. This study aims at providing insights into the structural as well as functional stability of this protein in Proteus vulgaris in these environments. Homology modelling coupled with molecular docking studies reveals that Cys785, Asp512, Phe685 and Phe691 are key residues in influencing the functionality of choline trimethylamine-lyase. Our findings demonstrate the optimum activity of the protein at alkaline conditions, thereby indicating the pathological potential of Proteus bacteria in the different dysbiotic states of the small and large intestines.