Publications (532) View all
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Dataset: Biosynthesis of gallic acid in Rhus typhina discrimination between alternative pathways from natural oxygen isotope abundance
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Article: The Lumazine synthase/Riboflavin synthase complex: Shapes and functions of a highly variable enzyme system.
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ABSTRACT: The xylene ring of riboflavin (vitamin B2 ) is assembled from two molecules of 3,4-dihydroxy-2-butanone 4-phosphate by a mechanistically complex process that is jointly catalyzed by lumazine synthase and riboflavin synthase. In Bacillaceae, these enzymes form a structurally unique complex comprising an icosahedral shell of 60 lumazine synthase subunits and a core of 3 riboflavin synthase subunits. Whereas many bacteria feature empty lumazine synthase capsids, fungi, Archaea and some eubacteria have pentameric lumazine synthases, and the riboflavin synthases of Archaea are paralogs of lumazine synthase. The structures of the molecular ensembles have been studied in considerable detail by X-ray crystallography, X-ray small angle scattering and electron microscopy. However, certain mechanistic aspects are still enigmatic. Surprisingly, the quaternary structure of the icosahedral β subunit capsids can undergo drastic changes resulting in the formation of large, quasispherical capsids; this process can be modulated by sequence mutations. The occurrence of those large shells consisting of 180 or more lumazine synthase subunits has recently generated interest for protein engineering topics, in particular for the construction of encapsulation systems. © 2013 The Authors Journal compilation © 2013 FEBS.FEBS Journal 04/2013; · 3.79 Impact Factor -
Article: Structures and reaction mechanisms of GTP cyclohydrolases.
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ABSTRACT: GTP cyclohydrolases generate the first committed intermediates for the biosynthesis of certain vitamins/cofactors (folic acid, riboflavin, deazaflavin, and tetrahydrobiopterin), deazapurine antibiotics, some t-RNA bases (queuosine, archaeosine), and the phytotoxin, toxoflavin. They depend on divalent cations for hydrolytic opening of the imidazole ring of the substrate, guanosine triphosphate (GTP). Surprisingly, the ring opening reaction is not the rate-limiting step for GTP cyclohydrolases I and II whose mechanism have been studied in some detail. GTP cyclohydrolase I, Ib, and II are potential targets for novel anti-infectives. Genetic factors modulating the activity of human GTP cyclohydrolase are highly pleiotropic, since the signal transponders whose biosyntheses require their participation (nitric oxide, catecholamines) impact a very wide range of physiological phenomena. Recent studies suggest that human GTP cyclohydrolase may become an oncology target. © 2013 IUBMB Life, 2013.International Union of Biochemistry and Molecular Biology Life 03/2013; · 3.51 Impact Factor -
Article: Structures of Fluoro, Amino, and Thiol Inhibitors Bound to the [Fe(4) S(4) ] Protein IspH.
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ABSTRACT: 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.Angewandte Chemie International Edition 01/2013; · 13.45 Impact Factor -
Article: Biosynthesis of the 22nd Genetically Encoded Amino Acid Pyrrolysine: Structure and Reaction Mechanism of PylC at 1.5Å Resolution.
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ABSTRACT: The second step in the biosynthesis of the 22nd genetically encoded amino acid pyrrolysine (Pyl) is catalyzed by PylC that forms the pseudopeptide l-lysine-N(ε)-3R-methyl-d-ornithine. Here, we present six crystal structures of the monomeric active ligase in complex with substrates, reaction intermediates, and products including ATP, the non-hydrolyzable ATP analogue 5'-adenylyl-β-γ-imidodiphosphate, ADP, d-ornithine (d-Orn), l-lysine (Lys), phosphorylated d-Orn, l-lysine-N(ε)-d-ornithine, inorganic phosphate, carbonate, and Mg(2+). The overall structure of PylC reveals similarities to the superfamily of ATP-grasp enzymes; however, there exist unique structural and functional features for a topological control of successive substrate entry and product release. Furthermore, the presented high-resolution structures provide detailed insights into the reaction mechanism of isopeptide bond formation starting with phosphorylation of d-Orn by transfer of a phosphate moiety from activated ATP. The binding of Lys to the enzyme complex is then followed by an S(N)2 reaction resulting in l-lysine-N(ε)-d-ornithine and inorganic phosphate. Surprisingly, PylC harbors two adenine nucleotides bound at the active site, what has not been observed in any ATP-grasp protein analyzed to date. Whereas one ATP molecule is involved in catalysis, the second adenine nucleotide functions as a selective anchor for the C- and N-terminus of the Lys substrate and is responsible for protein stability as shown by mutagenesis.Journal of Molecular Biology 09/2012; · 4.00 Impact Factor
