Inside Cover: Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non‐diphosphate Inhibitors (ChemBioChem 10/2017)

The inside cover picture shows the structure of the isoprenoid biosynthesis enzyme IspH with a newly discovered drug‐like inhibitor, a lipophilic barbiturate. IspH catalyzes the formation of ( E )‐1‐hydroxy‐2‐methylbut‐2‐enyl 4‐diphosphate, an essential enzyme in isoprenoid biosynthesis in most bacteria, malaria parasites, and plants. The results of spectroscopic studies (including HYSCORE and NRVS) led to a general model for ligand binding to IspH in which ligands bind directly to, or near to, the unique fourth Fe in the 4 Fe−4 S cluster. In silico screening of compound libraries led to new IspH inhibitors with ∼500 n m activity, potential leads for anti‐infectives and herbicides. More information can be found in the communication by E. Oldfield et al. on page 914 in Issue 10, 2017 (DOI: 10.1002/cbic.201700052).