Hofmann Laboratory

Research

Update: 28.01.2024

General Research Interests

Research in our laboratory focusses at understanding structure-function relationships of proteins involved in infectious diseases and addresses the problem of resistance to antibiotics occurring in parasitic, bacterial and fungal organisms.

Capitalising on genome and transcriptome data we seek to identify proteins involved in pathogen resistance in order to improve strategies of control and to develop therapeutic avenues by targeting novel pathogen proteins and interfering with pathogen-host interactions.

Using rigorous biochemical, biophysical, structural and computational methodologies, we conduct structure-function studies to obtain a solid understanding of molecular mechanisms with the clear aim of developing novel chemo- and immunotherapeutics.

The central aspect of all our projects is the three-dimensional structure of proteins and their complexes which is experimentally determined by protein X-ray crystallography and forms the basis to understand mechanisms on the molecular level. We further develop bio- and chemoinformatics software to underpin research work in this area and make these tools freely available to the community.

Projects

Annexins	European Annexin Homepage Annexin Structure-Function Allostery as a common annexin feature (Review) From Structure to Function (Review) Annexin-Benzodiazepine Interactions Annexin-Membrane Interactions Membrane-bound annexin A1 N-terminal peptides Liposomes in assessment of annexin-membrane interactions (Review) The Annexin A3-Membrane Interaction is Modulated by an N-Terminal Tryptophan Voltage-Dependent Binding of Annexins to Membranes Plant Annexins Structure, function and membrane interactions of plant annexins: an update (Review) Zea mays annexins modulate cytosolic free calcium Calcium-bound structure of cotton annexin Gh1 (PDB: 3BRX) Structural determinants for plant annexin -membrane interactions Annexins in the plant kingdom: perspectives and potentials (Review) Annexin Gh1 from Gossypium hirsutum (PDB: 1N00) Plant annexins form calcium-independent oligomers in solution Annexin 24 from Capsicum annuum (PDB: 1DK5) Parasite Annexins Biochemical characterisation of annexin B1 from Cysticercus cellulosae Parasite annexins - new molecules with potential for drug and vaccine development (Review) Unusual calcium-regulated mechanisms of alpha-1 giardin (PDB: 4EVF, 4EVH) Phylogeny of annexins from parasitic organisms and their vectors Structure and immunobiochemical characterisation of annexin B22 from Schistosoma mansoni (PDB: 4MDU, 4MDV) Membrane-associated tegument molecules of schistosome parasites (Review) Molecular characterisation of Schistosoma mansoni tegument annexins
Bioactive Compounds	(2S,4R,5S)-2,4-Dimethyl-5-hexanolide: Trail Pheromone for different Camponotus Species Dihydro-β-agarofurans Bioactive dihydro-β-agarofuran sesquiterpenes from Maytenus bilocularis Dihydro-β-agarofurans as leucine transport inhibitors Dihydro-β-agarofurans from the Australian rainforest vine Celastrus subspicata Dihydro-β-agarofurans from the Australian rainforest tree Maytenus bilocularis UHPLC-MS profiling for dihydro-β-agarofurans
Biochemical Assays	HPLC-based guanosine monophosphate kinase assay
Cyclic Nucleotide Phosphodiesterases	Cyclic Nucleotide Phosphodiesterase from Arabidopsis thaliana Semi-reduced (PDB: 1JH6) and Inhibitor-bound (PDB: 1JH7) Forms (Paper) Oxidised Form (PDB: 1FSI) Biophysical characterisation of three Cyclic Nucleotide Phosphodiesterases ASCH-domain containing protein from Zymomonas mobilis
Cytoskeletal Proteins	Cyclase-associated protein (CAP) Crystallisation of cyclase-associated protein from D. discoideum The orthorhombic crystal structure of CAP (PDB: 1TJF) Mechanism of oligomerisation Coronins Coronin structure and implications (Review) Coronin 3 (CRN3) involvement in F-actin dependent processes at the cell cortex Novel coronin-1C (CRN2) isoforms Phosphorylation of coronin-1C (CRN2) regulates F-actin and Arp2/3 interaction
Data Science	Machine learning approach to prediction of essential genes in D. melanogaster ML-based prediction of essential genes
Drug Discovery and Design	Carbonic anhydrases S-glycosyl primary sulfonamides for selective inhibition of cancer-associated carbonic anhydrases (PDB: 3HKN, 3HKQ, 3HKT, 3HKU) Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases (PDB: 3nb5, 3p4v) Ferrocene and ruthenocene-based enzyme inhibitors (PDB: 3P55,3p3h,3p44,3P3J) Non-classical β-carbonic anhydrase inhibitors Redox regulation of the β-carbonic anhydrase Rv1284 (PDB: 4YF4, 4yf5, 4yf6) Dichloro-naphthoquinone as a non-classical inhibitor of Rv3588c Compound screening assays Low cost whole-organism screening of compounds for anthelmintic activity Whole-organism motility assay: a step-by-step protocol Computational approaches Protein Fold Topology: Similar interactions of natural products with biosynthetic enzymes and therapeutic targets Panel docking as a means to improve efficiency of lead compound discovery A novel scaffold for DPP-4 inhibition Haemonchus contortus Selenophene and thiophene-core estrogen receptor ligands as inhibitors of H. contortus development Anthelmintic activity of novel pyrazole-5-carboxamide derivatives Rotenoids with potent nematocidal activity Nematocidal activity of deguelin Arylpyrrole analogues inhibiting H. contortus motility and development 1-Methyl-1H-pyrazole-5-carboxamides as high potency inhibitors of the barber’s pole worm Novel 1-methyl-1H-pyrazole-5-carboxamide derivatives with potent anthelmintic activity α-pyrones with anthelmintic activity against H. contortus Tetrahydroquinoxalines induce a lethal evisceration phenotype in H. contortus in vitro Tolfenpyrad analogues as inhibitors of H. contortus development Fromiamycalin and halaminol A display anthelmintic activity SAR of pyrrolidine-oxadiazoles as anthelmintics against H. contortus Kavalactone analogues with anthelmintic activity Natural compounds from the marine brown alga C. cephalornithos with anthelmintic activity Marine sponge extracts with anthelmintic activity Dysidenin affects the motility and morphology of H. contortus Identification of a parasite-speciﬁc target for an anthelmintic compound Structure-activity relationship of ABX464 in a model parasitic nematode, and target deconvolution Screening of compound libraries A novel hit compound with potential as broad-spectrum anthelmintic Target prediction Target prediction for ABX464 analogues in Caenorhabditis elegans
Electron Transfer and Redox	Ferredoxin-NADP⁺ Reductase from Capsicum annuum (PDB: 1SM4) S-nitrosylation of the Arabidopsis thaliana salicylic acid binding protein 3
Java Applications	PCSB – Program Collection for Structural Biology and Biophysical Chemistry (Web site) ACDP – a Java application for data processing and analysis of protein circular dichroism spectra DMAN – a Java tool for analysis of multi-well differential scanning fluorimetry experiments SBAL – a practical tool to generate and edit structure-based amino acid sequence alignments SDAR – a Java program for graphical analysis of 2D data MolScat and SAFIR – two Java tools for for small-angle X-ray scattering analysis of biomolecules ASSP – a Java application for secondary structure analysis from PDB files cApp – a practical tool for compound appraisal jBar - a tool for bivariate data analysis and bar graph plotting with R cDraw – a Java chemical drawing software DRfit – analysis of discrete data from multi-well plate assays
Overview	Impact of 'omic technologies on canine vector borne diseases Structural Chemistry at Eskitis Relevance of structural biology for studying parasite-host interactions Impact of next-generation technologies on exploration of parasites and development of new interventions Schistosomal proteins as targets for new therapeutics Human toxocariasis An epidemiological view at human toxocariasis Elucidating the molecular and developmental biology of parasitic nematodes Global prevalence of Toxocara infection in dogs Discovery of anthelmintics targeting the barber's pole worm Global and regional seroprevalence estimates for human toxocariasis – a call for action Global prevalence of Toxocara infection in cats Global prevalence of Toxascaris leonina infection in dogs and cats Harnessing natural product scaffolds for new anthelmintics
Prohibitins	Molecular modelling of prohibitin domains Towards understanding the roles of prohibitins (Review)
Proteins for Biotechnological Applications and Protein Engineering	Cyclised green fluorescent protein (PDB: 1KP5) β-glucosidase A from the halothermophile Halothermothrix orenii (PDB: 3TA9) Ribokinase from the halothermophile Halothermothrix orenii Minimal intact methyltransferase of a type I restriction-modification system
Proteins in Infectious Diseases	Genome, transcriptome and proteome studies The genome of Schistosoma haematobium Transcriptome and ES proteome of adult Fascioloides magna Transcriptome of Angiostrongylus vasorum Genome and transcriptome of Haemonchus contortus Comparative analyses of the transcriptomes of the lungworms Dictyocaulus filaria and D. viviparus Genome and transcriptome of the porcine whipworm Trichuris suis The genome of Opisthorchis viverrini The genetic blueprint of Toxocara canis Lucilia cuprina genome unlocks parasitic fly biology The Haemonchus contortus complement of M1 aminopeptidases Genome-wide diversity in Schistosoma japonicum Diversity in the Trichinella taxa Molecular alterations in the L3/L4 switch of Haemonchus contortus Specific dauer-like signalling pathway components in Toxocara canis Developmental phosphoproteome of Haemonchus contortus Draft genome of Dipylidium caninum Chromosome-contiguous Echinococcus granulosus (genotype G1) genome Ubiquitination pathway model for the barber's pole worm - Haemonchus contortus Parasite-specific phosphatases and kinases Glc seven-like phosphatase (gsp) orthologue from Haemonchus contortus Serine/threonine phosphatases in socioeconomically important parasitic nematodes (Research Review) Drug targets defined by the Schistosoma haematobium kinome The Haemonchus contortus kinome RIO kinases Atypical (RIO) protein kinases from Haemonchus contortus (Research Review) Bioinformatic exploration of RIO protein kinases of parasitic and free-living nematodes Analysis of RIO kinases in C. elegans Flatworms have lost the right open reading frame kinase 3 gene during evolution SCP/TAPS Proteins SCP/TAPS proteins of eukaryotes (Research Review) Hookworm SCP/TAPS protein structure (Research Review) (PDB: 3S6S, 3S6U, 3S6V) SCP/TAPS proteins of liver flukes Probing the equatorial groove (PDB: 4NUI, 4NUK, 4NUN, 4NUO) Na-ASP-2 involved in B cell receptor signalling SCP/TAPS proteins of Haemonchus contortus SCP/TAPS proteins of Toxocara canis Trehalose-6-phosphate phosphatases Molecular groupings of trehalose-6-phosphate phosphatases Enzyme characteristics of pathogen-specific trehalose-6-phosphate phosphatases Trehalose-6-phosphate phosphatase as a broad-spectrum therapeutic target Trehalose-6-phosphate phosphatases of Pseudomonas aeruginosa (PDB: 6cj0, 6D3V, 6D3W) A suicide inhibitor of nematode trehalose-6-phosphate phosphatases Trehalose-6-phosphate phosphatases from bacterial organisms Magnetic properties of schistosome eggshells Saposin-like proteins SLP-1 from human and dog hookworm (PDB: 3S63, 3S64) TIMPs in parasitic helminths Point mutations in Giardia triose-phosphate isomerase Scabies mite inactive serine proteases Lysosome-associated membrane glycoprotein from schistosomes A helminth chitinase with immunomodulatory properties Crystal structure of Mycobacterium bovis MurC (PDB: 7BVA, 7BVB) Crystal structure of Campylobacter jejuni MlghC (PDB: 7CXT)
Protein–Membrane Interactions	α1 integrin cytoplasmic tail interacts with phosphoinositides
Proteins in Neurological Diseases	Valosin-containing Protein (VCP) Pathological consequences of VCP mutations Strumpellin is a novel VCP binding protein VCP and PSMF1: antagonistic regulators of proteasome activity Species-specific changes in mutant VCP alter ATPase activity and compromise UBXD9-mediated monomerisation Genetic analysis of VCP and WASH-complex genes in a German cohort of sporadic ALS-FTD patients Strumpellin N471D leads to defects in the endolysosomal system Multisystem proteinopathy due to a homozygous p.Arg159His VCP mutation N471D WASH complex subunit strumpellin knock-in mice UBXD9–VCP protein interactions Visinin-like Proteins (VILIPs) Structure, function and expression of VILIPs (Review) VILIP-1, a Novel Regulator of the Guanylate Cyclase Transduction System in Neurons (Review) Interactions of VILIPs with phospho-inositides Divalent cations and redox conditions regulate VILIP-1 VILIP-1 and VILIP-3 binding to phospholipid monolayers Specific interactions of the N-terminal polybasic cluster of VILIPs Docking screens with the human subtype-D2 receptor
Vaccine Design	Streptococcal M protein Group A streptococcal M protein: improved vaccine candidate A new polyvalent group A streptococcal vaccine Predicted coverage and immuno-safety of a recombinant C-repeat region based vaccine candidate