title: Molecular insights of SAH enzyme catalysis and implication for inhibitor design.
abstract: Biological transmethylation reaction is a key step in the duplication of virus life cycle, in which S-adenosylmethionine plays as the methyl donor. The product of this reactions, S-adenosylhomocysteine (AdoHcy) inhibits the transmethylation process. AdoHcy is hydrolysed to adenosine and L-homocysteine by the action of S-adenosylhomocysteine hydrolase (SAH). Thus the virus life cycle should be cut off once the action of SAH is inhibited. Our study was focussed on the discovery of potential inhibitor against SAH. We performed a similarity search in Traditional Chinese Medicine Database and retrieved 17 hits with high similarity. After that we virtually docked the 17 compounds as well as the natural substrates to the hydrolase using Autodock 3.0.1 software. Then we discussed about the mechanism of the inhibition reaction, followed by proposing the potential inhibitors by comparing best docked solutions and possible modification for the best inhibitors.
authors.affiliation: College of Life Sciences and Biotechnology, Shanghai Jiaotong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China.
authors.forename: Huachun
authors.initials: H
authors.lastname: Wei
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Chunfang
authors.initials: C
authors.lastname: Wang
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zheng
authors.forename: Aixiu
authors.initials: A
authors.lastname: Li
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Wei
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D016208:Databases, Factual; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008516:Medicine, Chinese Traditional; D008745:Methylation; D008958:Models, Molecular; D008968:Molecular Conformation; D012266:Ribose / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D012266:Ribose; D043383:Adenosylhomocysteinase; D000225:Adenine