title: Insight into the reaction mechanism of cis,cis-muconate lactonizing enzymes: a DFT QM/MM study.
abstract: MLEs derived from mycobacterium smegmatis and seudomonas fluorescens share ∼76% identity and have a very similar arrangement of catalytic residues in their active site configuration. However, while they catalyze the conversion of cis,cis-muconate to the same achiral product, muconolactone, studies in deuterated solvent surprisingly show that the cyclo-isomerization proceeds with the formation of a chiral product. In this paper we discuss the application of DFT QM/MM calculations on both MLEs, to our knowledge the first reported in the literature on this protein. We investigate the proposal that the base involved in the catalytic reaction is the lysine residue found at the end of the 2(nd) strand given: (a) that the lysine residue at the end of the 6(th) strand is in an apparently equally effective position to catalyze reaction and (b) that the structural related epimerase in-fact achieve their stereo-specific outcomes by relying on either the base from the 2(nd) or 6(th) strand.
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, 50 Phaholyothin Road, Chatuchak, Bangkok 10900, Thailand.
authors.forename: Tuanjai
authors.initials: T
authors.lastname: Somboon
authors.forename: Matthew Paul
authors.initials: MP
authors.lastname: Gleeson
authors.forename: Supa
authors.initials: S
authors.lastname: Hannongbua
mesh_terms: D002384:Catalysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019753:Intramolecular Lyases / Q000737:chemistry*; D008958:Models, Molecular; D020102:Mycobacterium smegmatis / Q000737:chemistry / Q000201:enzymology; D011487:Protein Conformation; D016958:Pseudomonas putida / Q000737:chemistry / Q000201:enzymology; D011789:Quantum Theory
chemical_list: D019753:Intramolecular Lyases; C021811:muconate cycloisomerase