Artículos de revistas
Mapping of suramin binding sites on the group IIA human secreted phospholipase A(2)
Fecha
2009Registro en:
BIOORGANIC CHEMISTRY, v.37, n.1/Mar, p.41-45, 2009
0045-2068
10.1016/j.bioorg.2009.01.002
Autor
VIEIRA, Davi Serradella
ARAGAO, Elisangela Aparecida
LOURENZONI, Marcos Roberto
WARD, Richard J.
Institución
Resumen
Suramin is a polysulphonated napthylurea used as an antiprotozoal/anthelminitic drug, which also inhibits a broad range of enzymes. Suramin binding to recombinant human secreted group IIA phospholipase A(2) (hsPLA(2)GIIA) was investigated by molecular dynamics simulations (MD) and isothermal titration calorimetry (ITC). MD indicated two possible bound suramin conformations mediated by hydrophobic and electrostatic interactions with amino-acids in three regions of the protein. namely the active-site and residues located in the N- and C-termini, respectively. All three binding sites are located on the phospholipid membrane recognition surface, suggesting that suramin may inhibit the enzyme, and indeed a 90% reduction in hydrolytic activity was observed in the presence of 100 nM suramin. These results correlated with ITC data, which demonstrated 2.7 suramin binding sites on the hsPLA(2)GIIA, and indicates that suramin represents a novel class of phosphohpase A(2) inhibitor. (C) 2009 Elsevier Inc. All rights reserved.