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Molecular Modeling of T. rangeli, T. brucei gambiense, and T. evansi Sialidases in Complex with the DANA Inhibitor
Author(s) -
Lima Anderson H.,
Souza Paulo R. M.,
Alencar Nelson,
Lameira Jerônimo,
Govender Thavendran,
Kruger Hendrik G.,
Maguire Glenn E. M.,
Alves Cláudio N.
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01380.x
Subject(s) - trypanosoma brucei , trypanosoma evansi , trypanosoma , biochemistry , biology , sialidase , sialic acid , enzyme , chemistry , trypanosomiasis , virology , neuraminidase , gene
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.