title: Isoprenoid Biosynthesis in Pathogenic Bacteria: Nuclear Resonance Vibrational Spectroscopy Provides Insight into the Unusual [4Fe-4S] Cluster of the E. coli LytB/IspH Protein.
abstract: 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.
authors.affiliation: Fachbereich Physik, TU Kaiserslautern, Erwin-Schrödinger-Strasse 46, 67653 Kaiserslautern (Germany).
authors.forename: Isabelle
authors.initials: I
authors.lastname: Faus
authors.affiliation: Fachbereich Physik, TU Kaiserslautern, Erwin-Schrödinger-Strasse 46, 67653 Kaiserslautern (Germany).
authors.forename: Annegret
authors.initials: A
authors.lastname: Reinhard
authors.affiliation: Fachbereich Physik, TU Kaiserslautern, Erwin-Schrödinger-Strasse 46, 67653 Kaiserslautern (Germany).
authors.forename: Sergej
authors.initials: S
authors.lastname: Rackwitz
authors.affiliation: Fachbereich Physik, TU Kaiserslautern, Erwin-Schrödinger-Strasse 46, 67653 Kaiserslautern (Germany).
authors.forename: Juliusz A
authors.initials: JA
authors.lastname: Wolny
authors.affiliation: P01, Petra III, DESY, Notkestrasse 85, D-22607 Hamburg (Germany).
authors.forename: Kai
authors.initials: K
authors.lastname: Schlage
authors.affiliation: P01, Petra III, DESY, Notkestrasse 85, D-22607 Hamburg (Germany).
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Wille
authors.affiliation: ESRF - The European Synchrotron, CS40220, 38043 Grenoble Cedex 9 (France).
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Chumakov
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East RM 2020, Salt Lake City, UT 84112 (USA).
authors.forename: Sergiy
authors.initials: S
authors.lastname: Krasutsky
authors.affiliation: Université de Strasbourg, UMR 7177 CNRS, Institut Le Bel, 4 rue Blaise Pascal, CS 90032, 67081 Strasbourg Cedex (France).
authors.forename: Philippe
authors.initials: P
authors.lastname: Chaignon
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East RM 2020, Salt Lake City, UT 84112 (USA).
authors.forename: C Dale
authors.initials: CD
authors.lastname: Poulter
authors.affiliation: Université de Strasbourg, UMR 7177 CNRS, Institut Le Bel, 4 rue Blaise Pascal, CS 90032, 67081 Strasbourg Cedex (France). mseemann@unistra.fr.
authors.forename: Myriam
authors.initials: M
authors.lastname: Seemann
authors.affiliation: Fachbereich Physik, TU Kaiserslautern, Erwin-Schrödinger-Strasse 46, 67653 Kaiserslautern (Germany). schuene@physik.uni-kl.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Schünemann
mesh_terms: D053898:Biosynthetic Pathways; D018360:Crystallography, X-Ray; D011756:Diphosphates / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D029968:Escherichia coli Proteins; D013729:Terpenes; D010088:Oxidoreductases; C109866:ispH protein, E coli
keywords: LytB(IspH); inhibitors; metalloenzymes; methylerythritol phosphate pathway; nuclear resonance vibrational spectroscopy