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Recent Submissions
Data for "Influence of ionic liquids on enzymatic asymmetric carboligations"
(N/A, 2025) El Harrar, Till; Gohlke, Holger
The asymmetric mixed carboligation of aldehydes catalyzed by thiamine diphosphate (ThDP)-dependent enzymes provides a sensitive system for monitoring changes in activity, chemo-, and enantioselectivity. While previous studies have shown that organic cosolvents influence these parameters, we now demonstrate that similar effects occur upon addition of water-miscible ionic liquids (ILs). In this study, six ThDP-dependent enzymes were analyzed in the presence of 14 ILs under comparable conditions to assess their influence on enzymatic carboligation reactions yielding 2-hydroxy ketones. ILs exerted a moderate to strong influence on activity and, more notably, altered enantioselectivity. (R)-selective reactions were generally stable upon IL addition, while (S)-selective reactions frequently showed reduced selectivity or even inversion to the (R)-enantiomer. The most significant change was observed for the ApPDC_E469G variant of pyruvate decarboxylase from Acetobacter pasteurianus, where the enantiomeric excess shifted from 86% (S) to 60% (R) in the presence of 9% (w/v) Ammoeng 102. Control experiments indicated that this shift was primarily due to the Ammoeng cation rather than the anion. To explore the molecular basis of this phenomenon, all-atom molecular dynamics (MD) simulations were performed on wild-type ApPDC and the E469G variant in Ammoeng 101 and Ammoeng 102. The simulations revealed that hydrophobic and hydrophilic regions of the Ammoeng cations interact with the (S)-selective binding pocket, thereby favoring formation of the (R)-product. These results highlight the potential of solvent engineering for modulating enzyme selectivity and demonstrate that MD simulations can capture functionally relevant enzyme–solvent interactions at the atomic level.
Chaperone/ETR1 Structural Models for: Molecular Mechanism and Structural Models of Protein-Mediated Copper Transfer to the Arabidopsis thaliana Ethylene Receptor ETR1 at the ER Membrane
(N/A, 2025) Dluhosch, Dominik; Kersten, Lisa Sophie; Minges, Alexander; Schott-Verdugo, Stephan; Gohlke, Holger; Groth, Georg
In plants, the gaseous plant hormone ethylene regulates a wide range of developmental processes and stress responses. The small unsaturated hydrocarbon is detected by a family of receptors (ETRs) located in the membrane of the endoplasmic reticulum, which rely on a monovalent copper cofactor to detect this hydrocarbon. The copper-transporting P-type ATPase RAN1 (HMA7), located in the same membrane, is known to be essential for the biogenesis of ETRs. Still, the precise molecular mechanism by which the receptors acquire their copper cofactor remains unclear. A recent study by our laboratory demonstrated a direct interaction between RAN1 and soluble copper chaperones of the ATX1 family with the model ethylene receptor ETR1, providing initial insights into the mechanism by which copper is transferred from the cytosol to the membrane-bound receptors. In this study, we further investigated these interactions with respect to the function of individual domains in complex formation. To this end, we combined biochemical experiments and computational predictions and unraveled the processes and mechanisms by which copper is transferred to ETR1 at the molecular level.
SQLite file for TopCysteineDB: A Cysteinome-wide Database Integrating Structural and Chemoproteomics Data for Cysteine Ligandability Prediction
(N/A, 2025-04) Bonus, Michele; Greb, Julian; Majmudar, Jaimeen D.; Boehm, Markus; Korczynska, Magdalena; Nazemi, Azadeh; Mathiowetz, Alan M.; Gohlke, Holger
Development of targeted covalent inhibitors and covalent ligand-first approaches have emerged as a powerful strategy in drug design, with cysteines being attractive targets due to their nucleophilicity and relative scarcity. While structural biology and chemoproteomics approaches have generated extensive data on cysteine ligandability, these complementary data types remain largely disconnected. Here, we present TopCysteineDB, a comprehensive resource integrating structural information from the PDB with chemoproteomics data from activity-based protein profiling experiments. Analysis of the complete PDB yielded 264,234 unique cysteines, while the proteomics dataset encompasses 41,898 detectable cysteines across the human proteome. Using TopCovPDB, an automated classification pipeline complemented by manual curation, we identified 787 covalent cysteines and systematically categorized other functional roles, including metal-binding, cofactor-binding, and disulfide bonds. Mapping residue-wise structural information to sequence space enabled cross-referencing between structural and proteomics data, creating a unified view of cysteine ligandability. For TopCySPAL, a machine learning model was developed, integrating structural features and proteomics data, achieving strong predictive performance (AUROC: 0.964, AUPRC: 0.914) and robust generalization to novel cases. TopCysteineDB and TopCySPAL are freely accessible through a webinterface, TopCysteineDBApp (https://topcysteinedb.hhu.de/), designed to facilitate exploration of cysteine sites across the human proteome. The interface provides an interactive visualization featuring a color-coded mapping of chemoproteomics data onto cysteine site structures and the highlighting of identified peptide sequences. It offers customizable dataset downloads and ligandability predictions for user-provided structures. This resource advances targeted covalent inhibitor design by providing integrated access to previously dispersed data types and enabling systematic analysis and prediction of cysteine ligandability.
Subacute thyroiditis – Is it really linked to viral infection? - Supplemental material
(The authors, 2025-01-22) Hans Martin Orth, Alexander Killer, Smaranda Gliga, Michael Böhm, Torsten Feldt, Björn-Erik O. Jensen, Tom Luedde, Rolf Kaiser, Martin Pirkl
This document includes additional figures for the study "Subacute thyroiditis – Is it really linked to viral infection?"
Loss of Bmal1 impairs the glutamatergic light input to the SCN in mice
(NA, 2024-12-03) Korkmaz, Hüseyin; Anstötz, Max; Wellinghof, Tim; Fazari, Benedetta; Hallenberger, Angelika; Bergmann, Ann Kathrin; Niggetiedt, Elena; Güven, Delal; Tundo-Lavalle, Federica; Purath, Fathima Faiba A.; Bochinsky, Kevin; Gremer, Lothar; Willbold, Dieter; von Gall, Charlotte; Ali, Amira A. H.
Introduction: Glutamate represents the dominant neurotransmitter that conveys the light information to the brain, including the suprachiasmatic nucleus (SCN), the central pacemaker for the circadian system. The neuronal and astrocytic glutamate transporters are crucial for maintaining efficient glutamatergic signaling. In the SCN, glutamatergic nerve terminals from the retina terminate on vasoactive intestinal polypeptide (VIP) neurons, which are essential for circadian functions. Up-to-date, little is known about the role of the core circadian clock gene, Bmal1, in glutamatergic neurotransmission of light signal to various brain regions. Methods: The aim of this study was to further elucidate the role of Bmal1 in glutamatergic neurotransmission from the retina to the SCN. We therefore examined the spontaneous rhythmic locomotor activity, neuronal and glial glutamate transporters, as well as the ultrastructure of the synapse between the retinal ganglion cells (RGCs) and the SCN in adult male Bmal1-/- mice. Results: We found that the deletion of Bmal1 affects the light-mediated behavior in mice, decreases the retinal thickness and affects the vesicular glutamate transporters (vGLUT1,2) in the retina. Within the SCN, the immunoreaction of vGLUT1,2, glial glutamate transporters (GLAST) and VIP was decreased while the glutamate concentration was elevated. At the ultrastructure level, the presynaptic terminals were enlarged and the distance between the synaptic vesicles and the synaptic cleft was increased, indicative of a decrease in the readily releasable pool at the excitatory synapses in Bmal1-/-. Conclusion: Our data suggests that Bmal1 deletion affects the glutamate transmission at the tripartite synapse between the ipRGCs and the VIP neurons in the SCN and affects the behavioral responses to light.
Training Data for "PlugNSeq: An Easy, Rapid, and Streamlined mRNA-Seq Data Analysis Pipeline Empowering Insightful Exploration with Well-Annotated Organisms, Requiring Minimal Bioinformatic Expertise"
(protocols.io, 2024) Mai, Hans-Jörg
Here, we provide training data for the PlugNSeq mRNA-Seq data analysis pipeline. It contains a total of 24 gzip-compressed archives containing the mRNA-Seq reads of a rice experiment (Kar, S., Mai, HJ. et al., 2024, doi: 10.1093/pcp/pcab018 ).
The experimental setup is as follows: Plants from the two rice accessions "Hacha" and "Lachit" were grown hydroponically in control medium, and then exposed to control conditions or excess iron for three days, respectively. We harvested the leaves, extracted total RNA and after mRNA enrichment, we performed RNA-Seq (Illumina).
The files represent the following samples:
[sample_file_name] >>> [accession] - [treatment] - [replicate] - [direction]
4_S5_L003_R1_001.fastq.gz >>> Hacha - excess Fe - 1 - forward
4_S5_L003_R2_001.fastq.gz >>> Hacha - excess Fe - 1 - reverse
5_S6_L003_R1_001.fastq.gz >>> Hacha - excess Fe - 2 - forward
5_S6_L003_R2_001.fastq.gz >>> Hacha - excess Fe - 2 - reverse
6_S7_L003_R1_001.fastq.gz >>> Hacha - excess Fe - 3 - forward
6_S7_L003_R2_001.fastq.gz >>> Hacha - excess Fe - 3 - reverse
10_S11_L003_R1_001.fastq.gz >>> Lachit - excess Fe - 1 - forward
10_S11_L003_R2_001.fastq.gz >>> Lachit - excess Fe - 1 - reverse
11_S12_L003_R1_001.fastq.gz >>> Lachit - excess Fe - 2 - forward
11_S12_L003_R2_001.fastq.gz >>> Lachit - excess Fe - 2 - reverse
12_S13_L003_R1_001.fastq.gz >>> Lachit - excess Fe - 3 - forward
12_S13_L003_R2_001.fastq.gz >>> Lachit - excess Fe - 3 - reverse
16_S17_L004_R1_001.fastq.gz >>> Hacha - control - 1 - forward
16_S17_L004_R2_001.fastq.gz >>> Hacha - control - 1 - reverse
17_S18_L004_R1_001.fastq.gz >>> Hacha - control - 2 - forward
17_S18_L004_R2_001.fastq.gz >>> Hacha - control - 2 - reverse
18_S19_L004_R1_001.fastq.gz >>> Hacha - control - 3 - forward
18_S19_L004_R2_001.fastq.gz >>> Hacha - control - 3 - reverse
22_S23_L004_R1_001.fastq.gz >>> Lachit - control - 1 - forward
22_S23_L004_R2_001.fastq.gz >>> Lachit - control - 1 - reverse
23_S24_L004_R1_001.fastq.gz >>> Lachit - control - 2 - forward
23_S24_L004_R2_001.fastq.gz >>> Lachit - control - 2 - reverse
24_S25_L004_R1_001.fastq.gz >>> Lachit - control - 3 - forward
24_S25_L004_R2_001.fastq.gz >>> Lachit - control - 3 - reverse
The total size of all 24 reads files is ca. 57 GB. The average individual file size is ca. 2.4 GB. These are paired-end reads. Thus, equally named files that only differ in "R1" (forward reads) or "R2" (reverse reads) in their names, form pairs. If you want to check how preprocessing and analysis of single-end reads works, you may only use files with "R1" in the name. If there is no "R2" partner file, they will automatically be treated as single-end reads by the scripts in the pipeline. The original data included root samples, which are not included here.
Furthermore, we provide sample configuration files as they must be filled by the user after preprocessing and quantification has finished. You may copy and paste the respective file to the destination folder, or use it as a template for your own values. Important: We provide a "configuration_samples.xlsx" file for analysis in paired-end mode (if you use all packed reads files provided here) and an equally named file for analysis in single-end mode (if you use only files with "R1" but not "R2" in the file name. In the configuration file for single-end mode analysis, the TSV files listed in column A all have "R1" in the file name, while the file names in column A of the configuration file for analysis in paired-end mode all have "RX" in the file name instead.
With the provided data, and given enough free disk space on your machine, you can easily explore the simplicity and efficiency of the PlugNSeq pipeline without requiring your own data.