title: A combined experimental and computational study of Vam3, a derivative of resveratrol, and Syk interaction.
abstract: Spleen tyrosine kinase (Syk) plays an indispensable role through preliminary extracellular antigen-induced crosslinking of Fc receptor (FcR) in the pathogenesis of autoimmune disorders, such as rheumatoid arthritis. In this study, we identify Vam3, a dimeric derivative of resveratrol isolated from grapes, as an ATP-competitive inhibitor of Syk with an IC50 of 62.95 nM in an in vitro kinase assay. Moreover, docking and molecular dynamics simulation approaches were performed to get more detailed information about the binding mode of Vam3 and Syk. The results show that 11b-OH on ring-C and 4b-OH on ring-D could form two hydrogen bonds with Glu449 and Phe382 of Syk, respectively. In addition, arene-cation interaction between ring-D of Vam3 and Lys402 of Syk was also observed. These results indicate that ring-C and D play an essential role in Vam3-Syk interaction. Our studies may be helpful in the structural optimization of Vam3, and also aid the design of novel Syk inhibitors in the future.
authors.affiliation: Key Lab of Tianjin Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China. jiangmingpumc@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Medical Experiment Education Department, Medical College of Nanchang University, Nanchang 330031, China. sirlrp@163.com.
authors.forename: Renping
authors.initials: R
authors.lastname: Liu
authors.affiliation: Key Lab of Tianjin Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China. chenying_tj@hotmail.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Lab of Tianjin Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China. qishengzheng@126.com.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Key Lab of Tianjin Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China. fansaijun@163.com.
authors.forename: Saijun
authors.initials: S
authors.lastname: Fan
authors.affiliation: Key Lab of Tianjin Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China. pharm8888@163.com.
authors.forename: Peixun
authors.initials: P
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000072377:Syk Kinase; D027843:Vitis / Q000737:chemistry
chemical_list: D001572:Benzofurans; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D013267:Stilbenes; C000598179:Vam3 compound; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D000077185:Resveratrol