Pathway-based Screening Strategy for Multitarget Inhibitors of Diverse Proteins in Metabolic Pathways
Figure 1
Overview of pathway-based screening strategy for identifying conserved binding environments and multitarget inhibitors of multiple proteins.
(A) The proteins in the shikimate pathway. (B) Chemical reactions of shikimate dehydrogenase (SDH) and shikimate kinase (SK). SDH converts 3-dehydroshikimate into shikimate using NAPDH and then SK converts shikimate into shikimate 3-phosphate by ATP. These three compounds share the same substructure (blue region). (C) Establishment of site-moiety maps of SDH and SK. A site-moiety map represents the binding environments of a protein binding site by anchors. (D) The site-moiety map alignment of SDH and SK for identifying the conserved binding environments (pathway anchors). (E) Pathway anchors of SDH and SK. Hydrogen-bonding and van der Waals anchors are colored in green and gray, respectively. (F) Pathway inhibitors identified by the pathway anchors.