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Genomics. 2014 Jan;103(1):107-13. doi: 10.1016/j.ygeno.2013.11.008. Epub 2013 Dec 5.

3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA Topoisomerase IB, as a new emerging pharmacological target.

Author information

1
Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece.
2
Laboratory of Biology, University of Athens School of Medicine, Greece; Cell and Gene Therapy Laboratory, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece.
3
Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece. Electronic address: skossida@bioacademy.gr.

Abstract

In the present study, an outline is proposed that may lead to specific drug design targeting of the Trypanosoma brucei DNA Topoisomerase IB. In this direction, an unequivocally specific platform was designed for the development of selective modulators. The designed platform is focused on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all available published genomes indicated a broad distribution of DNA topoisomerases across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the mechanism of the T. brucei DNA Topoisomerase IB. Based on the above, we propose a comprehensive in silico 3D model for the structure of the T. brucei DNA Topoisomerase IB. Our approach provides an efficient intergraded platform with both evolutionary and structural insights for the rational design of pharmacophore models as well as novel modulators as the anti-T. brucei DNA Topoisomerase IB agents with therapeutic potential.

KEYWORDS:

3D molecular modeling; DNA Topoisomerase IB; Evolutionary study; Trypanosoma brucei

PMID:
24316217
DOI:
10.1016/j.ygeno.2013.11.008
[Indexed for MEDLINE]
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