Molecular dynamics simulation of the gGAPDH-NAD(+) complex from Trypanosoma cruzi

Autor(es)

de Oliveira, Osmair Vital ^{[1, 2]} ; dos Santos, Jose Divino ^[3] ; Freitas, Luiz C. G. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Ctr Ciencias Exatas & Tecnol, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[2] Inst Fed Espirito Santo, BR-29106010 Vila Velha, ES - Brazil

^[3] Univ Estadual Goias, Anapolis, Go - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR SIMULATION; v. 38, n. 13, p. 1124-1131, 2012.
• Citações Web of Science: 0

Resumo

A 50-ns molecular dynamics simulation has been used to study the homotetramer of the enzyme glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH) complexes, from Trypanosoma cruzi, with nicotinamide adenine dinucleotide (NAD(+)) cofactors in aqueous solution. The root mean square deviation indicates that the overall structure of the homotetramer does not undergo significant change. The largest structural change observed was in the NAD(+) binding domain of subunit (chain) D; as a consequence, the NAD(+) cofactor was dislocated from its initial position. However, the other subunits were not affected, suggesting that the gGAPDH enzyme exhibits non-cooperative behaviour. Our simulation estimates that the NAD(+) binding domain rotates about 4.8 degrees relative to the catalytic domain in the apo-holo form transition. The hydrogen bond analysis reveals that the residues R12, I13, D38 and M39 are essential for gGAPDH-NAD(+) interaction. Furthermore, two promising cavities to be explored in drug design were found: one formed by residues I13, R12, T197, T199, E336 and Y339, and the other by residues C166, H194, R249, I13, R12, T197, T199, E336 and Y339. The results presented in this paper offer new insight into the search for inhibitors of the gGAPDH enzyme of T. cruzi protozoan. (AU)

• Processo FAPESP: 07/54381-4 - Simulação computacional de sistemas químicos complexos
• Beneficiário: Luiz Carlos Gomide Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Regular