Ligand binding to <i>Pf</i>SpdS.

Abstract

<p>(A) Pathways for substrates, products, and inhibitors. The enzyme is represented schematically by a black outline indicating its binding sites and their conformational changes upon ligand binding: left, MTA cavity (triangle; fully formed in the free enzyme, unchanged with bound ligands); middle, central aminopropyl cavity (distorted circle in the free enzyme; becomes circular with bound ligands); right, putrescine site plus distal aminopropyl cavity (distorted oval in the free enzyme; becomes rectangular with bound ligands, some of which do not fill the distal cavity completely). Coloring of schematically represented compounds follows the colored boxes in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163442#pone.0163442.g002" target="_blank">Fig 2</a>: aminopropyl donor substrate and its product, beige; polyamine substrates and products, green; inhibitors, blue. The double arrows show binding equilibria between forms; the single arrows indicate enzymatic reaction. Letters and numbers under each shape correspond to the classes defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163442#pone.0163442.t003" target="_blank">Table 3</a> and depicted in panel B. (B) Classification of ligands. Upper left, the schematic representation of the active site introduced in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163442#pone.0163442.g001" target="_blank">Fig 1</a> and used here to identify ligand-binding locations. Lower left box, the indicated substrates and products are shown as stick cartoons placed in the appropriate active-site locations; right box, representation as in the left box showing the active-site positions of the compounds listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163442#pone.0163442.t003" target="_blank">Table 3</a>. Numbers and letters below each entry correspond to classes defined in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163442#pone.0163442.t003" target="_blank">Table 3</a> and represented in panel A. Placements in the active-site locations are based on the respective crystal structures except for S_2a* and S_2b*, which are artificially positioned in the structure with dcAdoMet only based on structures P_2a and P_2b with MTA, and I_2b*, which is artificially positioned in the structure with dcAdoMet based on structure I_3a of NACD with MTA.</p