title: Molecular modeling of T. rangeli, T. brucei gambiense, and T. evansi sialidases in complex with the DANA inhibitor.
abstract: Trypanosomal (trans-) sialidases are enzymes that catalyze the transfer of sialic acid residues between host and parasite glycoconjugates. Herein, we have used homology modeling to construct the 3D structures of sialidases from Trypanosoma brucei and Trypanosoma evansi. Hybrid quantum mechanical/molecular mechanical molecular dynamics simulations were used to determine the interaction energy between the 2-deoxy-2,3-didehydro-N-acetylneuraminic acid inhibitor and the three sialidases studied here. Our results suggest that the two constructed enzymes share the same basic fold motive of the Trypanosoma rangeli crystallographic structure. In addition, quantum mechanical/molecular mechanical molecular dynamics simulations show that the 2-deoxy-2,3-didehydro-N-acetylneuraminic acid inhibitor forms a stronger complex with Trypanosoma rangeli than with Trypanosoma brucei and Trypanosoma evansi sialidases. Finally, the interaction energy by residues shows that the arginine triad plays a decisive role to complex 2-deoxy-2,3-didehydro-N-acetylneuraminic acid with the enzyme through hydrogen bonding.
authors.affiliation: Laboratório de Planejamento e Desenvolvimento de Fármacos, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, CP 11101, 66075-110 Belém, PA, Brazil.
authors.forename: Anderson H
authors.initials: AH
authors.lastname: Lima
authors.forename: Paulo R M
authors.initials: PR
authors.lastname: Souza
authors.forename: Nelson
authors.initials: N
authors.lastname: Alencar
authors.forename: Jerônimo
authors.initials: J
authors.lastname: Lameira
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
authors.forename: Glenn E M
authors.initials: GE
authors.lastname: Maguire
authors.forename: Cláudio N
authors.initials: CN
authors.lastname: Alves
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D014345:Trypanosoma / Q000201:enzymology*; D014346:Trypanosoma brucei brucei / Q000201:enzymology; D014349:Trypanosoma cruzi / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; C036137:2-deoxy-2,3-dehydro-N-acetylneuraminic acid; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid