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Specific inhibitions of annonaceous acetogenins on class II 3-hydroxy-3-methylglutaryl coenzyme A reductase from Streptococcus pneumoniae.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2011 Jun 01; Vol. 19 (11), pp. 3512-9. Date of Electronic Publication: 2011 Apr 20. - Publication Year :
- 2011
-
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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acetogenins chemical synthesis
Acetogenins pharmacology
Amino Acid Sequence
Binding Sites
Computer Simulation
Hydroxymethylglutaryl CoA Reductases genetics
Hydroxymethylglutaryl CoA Reductases metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors chemistry
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Kinetics
Molecular Sequence Data
Protein Structure, Tertiary
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Acetogenins chemistry
Hydroxymethylglutaryl CoA Reductases chemistry
Hydroxymethylglutaryl-CoA Reductase Inhibitors chemical synthesis
Streptococcus pneumoniae enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 19
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21550257
- Full Text :
- https://doi.org/10.1016/j.bmc.2011.04.019