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Isoprenoid Biosynthesis in Pathogenic Bacteria: Nuclear Resonance Vibrational Spectroscopy Provides Insight into the Unusual [4Fe‐4S] Cluster of the E. coli LytB/IspH Protein
Author(s) -
Faus Isabelle,
Reinhard Annegret,
Rackwitz Sergej,
Wolny Juliusz A.,
Schlage Kai,
Wille HansChristian,
Chumakov Aleksandr,
Krasutsky Sergiy,
Chaig Philippe,
Poulter C. Dale,
Seemann Myriam,
Schünemann Volker
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201502494
Subject(s) - biosynthesis , substrate (aquarium) , chemistry , stereochemistry , molecule , bacteria , terpenoid , resonance (particle physics) , crystallography , biochemistry , enzyme , biology , organic chemistry , physics , genetics , ecology , particle physics
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, ( E )‐4‐hydroxy‐3‐methylbut‐2‐en‐1‐yl diphosphate (HMBPP) and to the inhibitors ( E )‐4‐amino‐3‐methylbut‐2‐en‐1‐yl diphosphate and ( E )‐4‐mercapto‐3‐methylbut‐2‐en‐1‐yl diphosphate.