Structures of Fluoro, Amino, and Thiol Inhibitors Bound to the [Fe4S4] Protein IspH

Authors


  • This work was supported by the Hans-Fischer Gesellschaft, DFG (grant GR1861/5-1), American Heart Association, Midwest Affiliate Predoctoral Fellowship (10PRE4430022), and the National Institutes of Health (NIH) (grant GM065307). We are grateful to Dr. Florian Kraus for his valuable contribution to the manuscript and David Hartmann for the synthesis of the fluoro analogue of HMBPP. We also thank the staff of the X06SA-beamline at the Paul Scherrer Institute, Swiss Light Source, Villigen, Switzerland for help during data collection.

Abstract

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The iron–sulfur protein IspH catalyzes a key step in isoprenoid biosynthesis in bacteria and malaria parasites. Crystal structures of IspH complexed with three substrate analogues reveal their mode of binding and suggest new routes to inhibitor design.

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