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[摘要]：falciparum spermidine synthase, were identified by structure-based virtual screening. The binding of these compds. was exptl. verified by NMR techniques. Spermidine synthase, an enzyme involved in the polyamine pathway, has been suggested as a target for treating malaria. The virtual screening protocol combined 3D pharmacophore filtering, docking, and scoring, focusing on finding compds. predicted to form interactions mimicking those of a previously known binder. The virtual screen resulted in the selection of 28 compds. that were acquired and tested from 2.6 million starting structures. Two of the seven binders were predicted to bind in the amino substrate binding pocket. Both of these showed stronger binding upon addn. of methylthioadenosine, one of the two products of the enzyme, and a known binder and inhibitor. The five other compds. were predicted to bind in the part of the active site where the other substrate, decarboxylated S-adenosylmethionine, binds. These five compds. all competed for binding with methylthioadenosine. |
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