title: Molecular basis of the recognition of FMN by a HAD phosphatase TON_0338.
abstract: The haloalkaloic acid dehalogenase (HAD) phosphatase from Thermococcus onnurineus NA1 (TON_0338), has phosphatase activity the flavin mono-nucleotide (FMN). The molecular origin and structural motifs for the activity deficiency of double-tryptophan mutant have not been rationalized at atomic resolution. Molecular dynamics (MD) simulations and the molecular mechanics/Generalized-Born surface area (MM/GBSA) free energy calculations were used to explore the effects of mutations on the changes in both structural flexibility and conformational dynamics. The non-polar solvation energy plays an indispensable role in the binding process of TON_0338 and FMN. The tryptophan sandwich structure provides a primary function to anchor FMN and keeps FMN well bound to TON_0338. The double-tryptophan mutation has influences on the secondary structures of TON_0338 and changes the conformation, which would lead to reduced activity of W58A/W61A-FMN binding. The present study provides important insights into the structure-function relationships of TON_0338 protein, which could contribute to further understanding about the HAD phosphatases.
authors.affiliation: Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China.
authors.forename: Rui-Juan
authors.initials: RJ
authors.lastname: Niu
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130023, People's Republic of China; Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China. Electronic address: zhengqc@jlu.edu.cn.
authors.forename: Qing-Chuan
authors.initials: QC
authors.lastname: Zheng
authors.affiliation: Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China; School of Pharmaceutical Sciences, Jilin University, Changchun 130022, People's Republic of China.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
mesh_terms: D000135:Acid Phosphatase / Q000737:chemistry* / Q000378:metabolism*; D016000:Cluster Analysis; D005486:Flavin Mononucleotide / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D019712:Thermococcus / Q000201:enzymology*; D013816:Thermodynamics
chemical_list: D050505:Mutant Proteins; D005486:Flavin Mononucleotide; D000135:Acid Phosphatase
keywords: Double-tryptophan mutation; FMN; HAD phosphatase; MM/GBSA; Molecular dynamics simulation; TON_0338