A5077731909- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Blood Coagulation and Thrombosis Mechanisms
- Protease and Inhibitor Mechanisms
- RNA and protein synthesis mechanisms
- Enzyme Production and Characterization
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Signaling Pathways in Disease
- Metabolism and Genetic Disorders
- Polyamine Metabolism and Applications
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Venomous Animal Envenomation and Studies
- Bacteriophages and microbial interactions
- Blood properties and coagulation
- RNA modifications and cancer
- Vitamin K Research Studies
- Computational Drug Discovery Methods
- Biopolymer Synthesis and Applications
Martin Luther University Halle-Wittenberg
2014-2024
Luther University
2019-2022
Leibniz Institute of Plant Biochemistry
2010
National University of Singapore
2008
Institute of Biostructure and Bioimaging
2008
Philipps University of Marburg
1997-2006
Novo Nordisk (Germany)
2003
University of Michigan
2003
University of Florence
2002
University of Erfurt
2000
The synthesis of the catecholic siderophore bacillibactin is accomplished by nonribosomal peptide synthetase (NRPS) encoded dhb operon. DhbE responsible for initial step in synthesis, activation aryl acid 2,3-dihydroxybenzoate (DHB). stand-alone adenylation (A) domain DhbE, structure which presented here, exhibits greatest homology to other NRPS A-domains, acyl-CoA ligases and luciferases. It's solved three different states, without ligands ATP DHB (native state), with product DHB-AMP...
Incretins, endogenous polypeptide hormones released in response to food intake, potentiate insulin secretion from pancreatic beta cells after oral glucose ingestion (the incretin effect). This is signaled by the two peptide glucose-dependent insulinotropic (GIP) (also known as gastric inhibitory polypeptide) and glucagon-like 1 through binding activation of their cognate class 2 G protein-coupled receptors (GPCRs). Because effect lost or significantly reduced patients with type diabetes...
The structure of the ternary complex human alpha-thrombin with a covalently bound analogue fibrinopeptide A and C-terminal hirudin peptide has been determined by X-ray diffraction methods at 0.25 nm resolution. Fibrinopeptide folds in compact manner, bringing together hydrophobic residues that slot into apolar binding site alpha-thrombin. Fibrinogen residue Phe8 occupies aryl-binding thrombin, adjacent to fibrinogen Leu9 Val15 S2 subsite. species diversity is analysed respect its...
Abstract While 3D electron diffraction (3D-ED or microcrystal diffraction, MicroED) has emerged as a promising method for protein structure determination, its applicability is hindered by high susceptibility to radiation damage, leading decreasing signal-to-noise ratio in consecutive patterns that limits the quality (resolution and redundancy) of data. In addition, data completeness may be restricted due geometrical limitations current sample holders stages. this work, we introduce an...
Virtual screening of compound libraries is an alternative and complementary approach to high-throughput in the lead discovery process. A new strategy described search for possible leads human carbonic anhydrase II, applying a protocol several consecutive hierarchical filters involving preselection based on functional group requirements fast pharmacophore matching. suitable derived by sophisticated "hot spot" analysis binding site detect regions favorable protein−ligand interactions. In...
X-ray crystal structures of the adducts human carbonic anhydrase (hCA) isozyme II with derivatives incorporating a sulfamide or sulfamic acid moiety are reported. The absence C−SO2NH2 bond in first type compound can be exploited for design more potent and selective CA inhibitors. This study also explains why sulfate is several-orders-of-magnitude weaker inhibitor compared to sulfonamide/sulfamide moieties.
DltA, the D-alanine:D-alanyl carrier protein ligase responsible for initial step of lipoteichoic acid D-alanylation in Gram-positive bacteria, belongs to adenylation domain superfamily, which also includes acetyl-CoA synthetase and domains non-ribosomal synthetases. The two-step reaction catalyzed by these enzymes (substrate followed transfer reactive thiol group CoA or phosphopantheinyl prosthetic peptidyl proteins) has been suggested proceed via large scale rearrangements structural within...
Oligomers are intermediates of the β-amyloid (Aβ) peptide fibrillogenic pathway and putative pathogenic culprits in Alzheimer's disease (AD). Here we report biotechnological generation biochemical characterization an oligomer-specific antibody fragment, KW1. KW1 not only discriminates between oligomers other Aβ conformations, such as fibrils or disaggregated peptide; it also differentiates different types oligomers, those formed by (1-40) (1-42) peptide. This high selectivity binding...
Although site-specific incorporation of artificial functionalities into proteins is an important tool in both basic and applied research, it can be a major challenge to protein chemists. Enzymatic modification attractive goal due the inherent regio- stereoselectivity enzymes, yet their specificity remains problem. As result intrinsic reversibility enzymatic reactions, proteinases principle catalyze ligation reactions. While this makes them tools for bioconjugation, competing hydrolysis...
We have solved the 2.5-Å crystal structure of 1-deoxy-d-xylulose-5-phosphate reductoisomerase, an enzyme involved in mevalonate-independent 2-<i>C</i>-methyl-d-erythritol-4-phosphate pathway isoprenoid biosynthesis. The reveals that is present as a homodimer. Each monomer displays V-like shape and composed amino-terminal dinucleotide binding domain, connective carboxyl-terminal four-helix bundle domain. domain responsible for dimerization harbors most active site. strictly conserved acidic...
The trypsin-like serine proteinase superfamily contains a number of potential therapeutic targets, many which are unsuitable for routine X-ray crystallographic studies. We have cocrystallized selection benzamidine-based inhibitors with bovine trypsin and solved their structures to resolution up 1.7 A. Despite similar chemical formulas, the exhibit range diverse binding modes that reflect inhibitory spectra against proteinases trypsin, thrombin, factor Xa, tissue-type plasminogen activator...
Eubacterial tRNA-guanine transglycosylase (TGT) is involved in the hypermodification of cognate tRNAs, leading to exchange G34 by preQ1 at wobble position anticodon loop. Mutation tgt gene Shigella flexneri results a significant loss pathogenicity bacterium due inefficient translation virulence protein mRNA. Herein, we describe discovery ligand with an unexpected binding mode. On basis this mode, three slightly deviating pharmacophore hypotheses have been derived. Virtual screening based on...
Crystal structures of DX9065a and a related bisamidino‐aryl inhibitor specific for the blood‐clotting factor Xa have been solved in complex with bovine β‐trypsin to resolution 1.9 Å. Each exhibits an extended conformation along active site, contrast compact folded observed thrombin inhibitors. Few direct contacts (predominantly S1 pocket) are made between trypsin Transfer inhibitors site suggests three‐site interaction: salt bridge formation at base primary specificity pocket, extensive...
Abstract Multidrug resistance (MDR) poses a major challenge to medicine. A principle cause of MDR is through active efflux by transporters situated in the bacterial membrane. Here we present crystal structure facilitator superfamily (MFS) drug/H + antiporter MdfA from Escherichia coli an outward open conformation. Comparison with inward facing (drug binding) state shows that, addition expected change relative orientations N- and C-terminal lobes antiporter, conformation TM5 kinked twisted....
Significance During the earliest stages of fruit fly development, differentiation embryo into dorsal and ventral sections commences following localized initiation a proteolytic cascade that culminates in cleavage activation human nerve growth factor-like cystine knot protein Spätzle. In turn, this activated ligand activates Toll receptor, instigating an intracellular signal leads to location-specific cell differentiation. Both Spätzle are also integral pathogen recognition adult flies, where...