Premium
Frontispiece: Freezing the Dynamic Gap for Selectivity: Motion‐Based Design of Inhibitors of the Shikimate Kinase Enzyme
Author(s) -
Prado Verónica,
Lence Emilio,
Thompson Paul,
Hawkins Alastair R.,
GonzálezBello Concepción
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201685062
Subject(s) - shikimic acid , selectivity , shikimate pathway , enzyme , chemistry , biochemistry , stereochemistry , substrate (aquarium) , combinatorial chemistry , transferase , active site , catalysis , aromatic amino acids , biology , ecology
Inhibitors Enzymes are “dynamic” systems that are able to adopt diverse conformations during catalysis—an open conformation (OFF) for product release and a closed form (ON) for substrate conversion. In their Full Paper on page 17988 ff., C. González‐Bello et al. show how disabling the closure of the active site for catalysis is an alternative strategy for inhibitor design as well as for selectivity among homologous enzymes. They show that the incorporation of bulky groups at position C5 of 5‐aminoshikimic acid enhances the selectivity for shikimate kinase from Helicobacter pylori versus Mycobacterium tuberculosis due to key motion differences in the shikimic acid binding domain, which is highly conserved in the two bacterial enzymes.