title: Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase.
abstract: A three-dimensional structural model of nattokinase (NK) from Bacillus natto was constructed by homology modeling. High-resolution X-ray structures of Subtilisin BPN' (SB), Subtilisin Carlsberg (SC), Subtilisin E (SE) and Subtilisin Savinase (SS), four proteins with sequential, structural and functional homology were used as templates. Initial models of NK were built by MODELLER and analyzed by the PROCHECK programs. The best quality model was chosen for further refinement by constrained molecular dynamics simulations. The overall quality of the refined model was evaluated. The refined model NKC1 was analyzed by different protein analysis programs including PROCHECK for the evaluation of Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300ps long unconstrained molecular dynamics (MD) simulation. Further docking analysis promoted the coming of a new nucleophilic catalytic mechanism for NK, which is induced by attacking of hydroxyl rich in catalytic environment and locating of S221.
authors.affiliation: Key Laboratory of Virology (Wuhan University), Ministry of Education, Life Science's College of Wuhan University, Wuhan 430072, China.
authors.forename: Zhong-liang
authors.initials: ZL
authors.lastname: Zheng
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Zuo
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Liu
authors.forename: Keng-chang
authors.initials: KC
authors.lastname: Tsai
authors.forename: Ai-fu
authors.initials: AF
authors.lastname: Liu
authors.forename: Guo-lin
authors.initials: GL
authors.lastname: Zou
mesh_terms: D000595:Amino Acid Sequence; D001407:Bacillus / Q000201:enzymology*; D002384:Catalysis; D003198:Computer Simulation; D005343:Fibrinolytic Agents / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020860:Subtilisin / Q000737:chemistry; D013381:Subtilisins / Q000737:chemistry*
chemical_list: D005343:Fibrinolytic Agents; D013381:Subtilisins; D020860:Subtilisin; C053771:nattokinase