title: Specific inhibitions of annonaceous acetogenins on class II 3-hydroxy-3-methylglutaryl coenzyme A reductase from Streptococcus pneumoniae.
abstract: 3-Hydroxy-3-methylglutaryl coenzyme A reductase (class II HMGR) could serve as a potential target to discover drugs fighting against the invasive diseases originated from Streptococcus pneumoniae, one of the major causes of bacterial disease in human. However, no strongly effective inhibitors of class II HMGR have been found so far. In the present study, for the first time, four annonaceous acetogenins (ACGs) were explored for the inhibition on S. pneumoniae HMGR. The results showed that the ACGs had higher inhibitory activities against S. pneumoniae HMGR with K(i) values in the range of 6.45-20.49 μM than the statin drug lovastatin (K(i)=116.25 μM), a classical inhibitor of class I HMGR. Then, three-dimensional modeling and docking simulations analyzed the possible binding mode of ACGs to S. pneumoniae HMGR and suggested a kind of novel structural and binding mode for designing promising inhibitor candidates of the targeted enzyme S. pneumoniae II HMGR.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China. fll708@mail.ccnu.edu.cn
authors.forename: Lingling
authors.initials: L
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Gui
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Wan
authors.forename: Yanliang
authors.initials: Y
authors.lastname: Ren
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Qiu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D054378:Acetogenins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000201:enzymology*
chemical_list: D054378:Acetogenins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011994:Recombinant Proteins; D006903:Hydroxymethylglutaryl CoA Reductases