Inside Cover: Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non‐diphosphate Inhibitors (ChemBioChem 10/2017). (2nd May 2017)

• Record Type: Journal Article
• Authors: O'Dowd, Bing; Williams, Sarah; Wang, Hongxin; No, Joo Hwan; Rao, Guodong; Wang, Weixue; McCammon, J. Andrew; Cramer, Stephen P.; Oldfield, Eric
• Is Part Of: Chembiochem. Volume 18:Number 10(2017)
• Page Start: 882
• Page End: 882
• Publication Date: 2017-05-02
• Subjects: HYSCORE -- in silico -- isoprenoid -- IspH -- NRVS; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201700218
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract : 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 nm activity, potential leads for anti‐infectives and herbicides. More information can be found in the communication by E. Oldfield et al. onpage 914 in Issue 10, 2017 (DOI:10.1002/cbic.201700052 ).