Mapping of suramin binding sites on the group IIA human secreted phospholipase A2.

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Vieira DS, Aragao EA, Lourenzoni MR, Ward RJ

Mapping of suramin binding sites on the group IIA human secreted phospholipase A2.

Bioorg Chem. 2009 Apr;37(2):41-5. doi: 10.1016/j.bioorg.2009.01.002. Epub 2009 Feb 3.

PubMed ID

19251299 [ View in PubMed

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Abstract

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 100nM 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 phospholipase A(2) inhibitor.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Suramin	Cytosolic phospholipase A2	Protein	Humans	Unknown	Inhibitor	Details