Cambyz Irajie, Milad Mohkam , Bahareh Vakili and Navid Nezafat*
Background: L-Methioninase (EC 126.96.36.199; MGL) is a pyridoxal phosphate (PLP)-dependent enzyme that is produced by a variety of bacteria, fungi, and plants. L-methioninase, especially from Pseudomonas and Citrobacter sp. is considered as the efficient therapeutic enzymes, particularly in cancers such as glioblastomas, medulloblastoma, and neuroblastoma that are more sensitive to methionine starvation. Objective: The low stability is one of the main drawbacks of the enzyme; in this regard, in the current study, different features of the enzyme, including phylogenetic, functional, and structural from Pseudomonas, Escherichia, Clostridium, and Citrobacter strains were evaluated to find the best bacterial L-Methioninase.
Methods: After the initial screening of L-Methioninase sequences from the above-mentioned bacterial strains, the three-dimensional structure of enzymes from Escherichia fergusonii, Pseudomonas fluorescens, and Clostridium homopropionicum were determined through homology modeling via GalaxyTBM server and refined by GalaxyRefine server.
Results & Conclusion: Afterwards, PROCHECK, verify 3D, and ERRAT servers were used for verification of the obtained models. Moreover, antigenicity, allergenicity, and physico-chemical analysis of enzymes were also carried out. In order to get insight into interaction of enzyme with other proteins the STRING server was used. The secondary structure of enzyme is mainly composed of random coils and alpha-helices. However, these outcomes should further be validated by wet lab investigations.
L-Methioninase, In silico analysis, Escherichia, Pseudomonas, Clostridium, phylogenetic
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz