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Inside Cover: Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non‐diphosphate Inhibitors (ChemBioChem 10/2017)
Author(s) -
O'Dowd Bing,
Williams Sarah,
Wang Hongxin,
No Joo Hwan,
Rao Guodong,
Wang Weixue,
McCammon J. Andrew,
Cramer Stephen P.,
Oldfield Eric
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700218
Subject(s) - in silico , ligand (biochemistry) , chemistry , enzyme , stereochemistry , biosynthesis , drug discovery , drug target , terpenoid , biochemistry , computational biology , biology , receptor , gene
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).