Pyridine inhibitor binding to the 4Fe-4S protein A. aeolicus IspH (LytB): a HYSCORE Investigation

J Am Chem Soc. 2011 May 4;133(17):6525-8. doi: 10.1021/ja2008455. Epub 2011 Apr 12.

Abstract

IspH is a 4Fe-4S protein that carries out an essential reduction step in isoprenoid biosynthesis. Using hyperfine sublevel correlation (HYSCORE) spectroscopy, we show that pyridine inhibitors of IspH directly bind to the unique fourth Fe in the 4Fe-4S cluster, opening up new routes to inhibitor design, of interest in the context of both anti-bacterial as well as anti-malarial drug discovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Bacteria / metabolism*
  • Bacterial Proteins / metabolism*
  • Drug Design
  • Iron-Sulfur Proteins / metabolism*
  • Models, Molecular
  • Protein Binding
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Terpenes / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Iron-Sulfur Proteins
  • Pyridines
  • Terpenes
  • pyridine