title: 3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA Topoisomerase IB, as a new emerging pharmacological target.
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.
authors: Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece.
authors: Dimitrios
authors: D
authors: Vlachakis
authors: Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece.
authors: Athanasia
authors: A
authors: Pavlopoulou
authors: 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.
authors: Maria G
authors: MG
authors: Roubelakis
authors: Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece.
authors: Christos
authors: C
authors: Feidakis
authors: 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.
authors: Nikolaos P
authors: NP
authors: Anagnou
authors: Bioinformatics & Medical Informatics Team, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, Athens 11527, Greece. Electronic address: skossida@bioacademy.gr.
authors: Sophia
authors: S
authors: Kossida
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism*; D016054:DNA, Protozoan / Q000235:genetics; D016503:Drug Delivery Systems; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins; C475926:DNA topoisomerase IB, Trypanosoma brucei; D004264:DNA Topoisomerases, Type I
keywords: 3D molecular modeling; DNA Topoisomerase IB; Evolutionary study; Trypanosoma brucei