A5053088560- Plant biochemistry and biosynthesis
- Organometallic Compounds Synthesis and Characterization
- Metal complexes synthesis and properties
- Microbial Natural Products and Biosynthesis
- Crystal structures of chemical compounds
- Organometallic Complex Synthesis and Catalysis
- Polydiacetylene-based materials and applications
- Magnetism in coordination complexes
- Enzyme Structure and Function
- Synthesis and characterization of novel inorganic/organometallic compounds
- Photosynthetic Processes and Mechanisms
- Biochemical and Molecular Research
- Lanthanide and Transition Metal Complexes
- Microbial Metabolic Engineering and Bioproduction
- Fluorine in Organic Chemistry
- Porphyrin and Phthalocyanine Chemistry
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Organophosphorus compounds synthesis
- Chemical Synthesis and Analysis
- Inorganic and Organometallic Chemistry
- Asymmetric Hydrogenation and Catalysis
- Ferrocene Chemistry and Applications
- Natural product bioactivities and synthesis
- Organic and Molecular Conductors Research
- Polyoxometalates: Synthesis and Applications
University of Freiburg
2019
Technical University of Munich
2002-2011
Center for Integrated Protein Science Munich
2011
Pennsylvania State University
2010
Leibniz-Institute for Food Systems Biology at the Technical University of Munich
2006
Universität Hamburg
2006
ETH Zurich
2002-2004
Freie Universität Berlin
2004
Schiller International University
1989
Iowa State University
1988
Earlier in vivo studies have shown that the sequential action of IspG and IspH proteins is essential for reductive transformation 2C-methyl-d-erythritol 2,4-cyclodiphosphate into dimethylallyl diphosphate isopentenyl via 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. A recombinant fusion protein comprising maltose binding domains was purified from a Escherichia coli strain. The failed to transform 4-diphosphate, but catalytic activity could be restored by addition crude cell extract an...
2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in methylerythritol phosphate pathway, which represents an alternative route classical mevalonate pathway. As it present many pathogens and plants, but not man, this pathway has attracted considerable interest as a target for novel antibiotics herbicides. Fosmidomycin specific high-affinity inhibitor of IspC. Very recently, its anti-malaria activity man been demonstrated clinical...
Earlier in vivo studies showed the involvement of IspH protein conversion 1-hydroxy-2-methyl-2-( E )-butenyl 4-diphosphate into isopentenyl diphosphate (IPP) and dimethylallyl (DMAPP). We have demonstrated now that cell extract an Escherichia coli strain engineered for hyperexpression ispH ( lytB ) gene catalyzes vitro IPP DMAPP. The reaction requires NADH, FAD, divalent cations (preferably Co 2+ ), probably one or more as-yet-unidentified proteins. low intrinsic catalytic activities...
Abstract The lattice‐controlled solid‐state polymerisation of three different modifications 2,4‐hexadiin‐1,6‐diol‐bis(phenylurethane) was investigated by X‐ray and optical methods. is a homogeneous reaction. polymer grows in the form single chains within crystal monomer. extend along definite crystallographic direction. Monomer are isomorphous monomer‐polymer crystals various compositions obtained up to quantitative conversion case modification I or III. Phase separation into mesomorphic...
The ispH gene of Escherichia coli specifies an enzyme catalyzing the conversion 1-hydroxy-2-methyl-2-(E)-butenyl diphosphate into a mixture isopentenyl (IPP) and dimethylallyl (DMAPP) in nonmevalonate isoprenoid biosynthesis pathway. implementation cassette directing overexpression isc operon involved assembly iron−sulfur clusters strain engineered for expression increased catalytic activity IspH protein anaerobically purified from this by factor at least 200. For maximum activity,...
<h3>Background and objectives</h3> Hepatocellular carcinoma (HCC) affects an increasing number of people worldwide. The poor survival rate patients with HCC is manifested by aggressive metastatic phenotype, as well a response to common therapeutic strategies. purpose this study was evaluate the efficacy nanoliposomal C6-ceramide antineoplastic agent in vivo model human HCC. <h3>Methods</h3> growth-arresting pro-apoptotic properties were first evaluated vitro SK-HEP-1 cells assessing cellular...
Abstract Die Kristallstruktur von Bis(1,1‐diäthyl‐3‐benzoyl‐thioureato)palladium(II) wurde durch Röntgeneinkristallstrukturanalyse bestimmt. Verbindung kristallisiert monoklin, Raumgruppe P2 1 /n mit a = 13,63, b 19,88, c 10,48 Å, β 101,4° Z 4. Struktur Hilfe der Schweratommethode gelöst und bis zu einem R‐Wert 0,12 verfeinert. S‐ O‐Ligatoratome sind in cis‐Stellung angeordnet. Alle PdS‐ PdO‐Abstände unterschiedlich lang. Chelatringe eben gebaut.
Abstract A library of 40 000 compounds was screened for inhibitors 2‐methylerythritol 2,4‐cyclodiphosphate synthase (IspF) protein from Arabidopsis thaliana using a photometric assay. thiazolopyrimidine derivative resulting the high‐throughput screen found to inhibit IspF proteins Mycobacterium tuberculosis , Plasmodium falciparum and A. with IC 50 values in micromolar range. Synthetic efforts afforded derivatives that M. P. low Several act as weak red blood cell
Abstract Bis(1,1‐diäthyl‐3‐benzoyl‐thioureato) kupfer(II) existiert in drei monoklinen Modifikationen, deren kristallographische Daten ermittelt wurden. Die Kristall‐ und Molekül‐struktur einer der Modifikationen wurde mittels Röntgenkristallstrukturanalyse bestimmt. Diese Modifikation kristallisiert monoklin Raumgruppe P2 1 /c mit den Gitterkonstanten a = 8,871, b 29,492, c 12,281 Å, β 124,50° 4 Formeleinheiten pro Elementarzelle. Struktur Schweratommethode gelöst bis zu einem R‐Wert von R...
Reverse hydroxamate-based inhibitors of IspC, a key enzyme the non-mevalonate pathway isoprenoid biosynthesis and validated antimalarial target, were synthesized biologically evaluated. The binding mode one derivative in complex with EcIspC divalent metal ion was clarified by X-ray analysis. Pilot experiments have demonstrated vivo potential.
The pick of the pockets: first inhibitors for IspD, an enzyme from non-mevalonate pathway isoprenoid biosynthesis, are described. High-throughput-screening revealed a hit with IC50 value 140 nM. Co-crystal structure analyses binding mode in newly formed allosteric pocket (see structure, red ball: water O atom), lead to synthesis set 17 derivatives which were tested optimize herbicidal activity. Detailed facts importance specialist readers published as "Supporting Information". Such documents...
An open reading frame (Acc. no. P50740) on the Bacillus subtilis chromosome extending from bp 184 997–186 043 with similarity to idi‐2 gene of Streptomyces sp. CL190 specifying type II isopentenyl diphosphate isomerase was expressed in a recombinant Escherichia coli strain. The protein subunit mass 39 kDa purified apparent homogeneity by column chromatography. shown catalyse conversion dimethylallyl into and vice versa at rates 0.23 0.63 µmol·mg −1 ·min , respectively, as diagnosed 1 H...
The nonmevalonate isoprenoid pathway is an established target for antiinfective drug development. This paper describes high-throughput methods the screening of 2C-methyl-d-erythritol synthase (IspC protein), 4-diphosphocytidyl-2C-methyl-d-erythritol (IspD kinase (IspE and 2,4-cyclodiphosphate (IspF protein) against large compound libraries. assays use up to three auxiliary enzymes. They are all monitored photometrically at 340 nm robust as documented by Z-factors ≥0.86. 13C NMR designed hit...
The IspG protein is known to catalyze the transformation of 2-C-methyl-d-erythritol 2,4-cyclodiphosphate into 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate in nonmevalonate pathway isoprenoid biosynthesis. We have found that apparent activity cell extracts recombinant Escherichia coli cells as observed by a radiochemical assay can be enhanced severalfold coexpression isc operon which involved assembly iron−sulfur clusters. was isolated affinity chromatography under anaerobic conditions....
GTP cyclohydrolase II catalyzes the hydrolytic release of formate and pyrophosphate from producing 2,5‐diamino‐6‐ribosylamino‐4(3 H )‐pyrimidinone 5′‐phosphate, first committed intermediate in biosynthesis riboflavin. The enzyme was shown to contain one zinc ion per subunit. Replacement cysteine residue 54, 65 or 67 with serine resulted proteins devoid bound unable imidazole ring analog, 2‐amino‐5‐formylamino‐6‐ribosylamino‐4(3 5′‐triphosphate. However, mutant retained capacity...
The ispC gene of Arabidopsis thaliana was expressed in pseudomature form without the putative plastid-targeting sequence a recombinant Escherichia coli strain. protein purified by affinity chromatography and shown to catalyze formation 2C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate at rate 5.6 micromol x min(-1) mg(-1) (k(cat) 4.4 s(-1)). Michaelis constants for cosubstrate NADPH are 132 30 microm, respectively. enzyme has an absolute requirement divalent metal ions,...
Designed inhibitors (like 1) of IspF, a key enzyme in the non-mevalonate pathway for terpene biosynthesis and potential antimalarial target, were synthesized evaluated. Since fluorescent probes introduced these ligands, their affinity towards IspF from E. coli could be determined by fluorescence titrations. The binding modes two ligands ternary complexes with ZnII ion clarified X-ray analysis.