Isoprenoid Biosynthesis in Pathogenic Bacteria: Nuclear Resonance Vibrational Spectroscopy Provides Insight into the Unusual [4Fe‐4S] Cluster of the E. coli LytB/IspH Protein1. Issue 43 (26th June 2015)

• Record Type: Journal Article
• Authors: Faus, Isabelle; Reinhard, Annegret; Rackwitz, Sergej; Wolny, Juliusz A.; Schlage, Kai; Wille, Hans‐Christian; Chumakov, Aleksandr; Krasutsky, Sergiy; Chaignon, Philippe; Poulter, C. Dale; Seemann, Myriam; Schünemann, Volker
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 43(2015)
• Page Start: 12584
• Page End: 12587
• Publication Date: 2015-06-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201502494
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The LytB/IspH protein catalyzes the last step of the methylerythritol phosphate (MEP) pathway which is used for the biosynthesis of essential terpenoids in most pathogenic bacteria. Therefore, the MEP pathway is a target for the development of new antimicrobial agents as it is essential for microorganisms, yet absent in humans. Substrate‐free LytB has a special [4Fe‐4S]²⁺ cluster with a yet unsolved structure. This motivated us to use synchrotron‐based nuclear resonance vibrational spectroscopy (NRVS) in combination with quantum chemical‐molecular mechanical (QM/MM) calculations to gain more insight into the structure of substrate‐free LytB. The apical iron atom of the [4Fe‐4S]²⁺ is clearly linked to three water molecules. We additionally present NRVS data of LytB bound to its natural substrate, (<italic>E</italic>)‐4‐hydroxy‐3‐methylbut‐2‐en‐1‐yl diphosphate (HMBPP) and to the inhibitors (<italic>E</italic>)‐4‐amino‐3‐methylbut‐2‐en‐1‐yl diphosphate and (<italic>E</italic>)‐4‐mercapto‐3‐methylbut‐2‐en‐1‐yl diphosphate.</p> </abstract>