A5050783675- Enzyme Structure and Function
- Plant biochemistry and biosynthesis
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Microbial Metabolic Engineering and Bioproduction
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Metabolism and Genetic Disorders
- Neurological diseases and metabolism
- Microbial Natural Products and Biosynthesis
- Protein Tyrosine Phosphatases
- Erythrocyte Function and Pathophysiology
- Bone Metabolism and Diseases
- Cell Adhesion Molecules Research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Click Chemistry and Applications
- Protein Interaction Studies and Fluorescence Analysis
- Heat shock proteins research
- Porphyrin Metabolism and Disorders
- Protease and Inhibitor Mechanisms
- Pharmacological Effects of Natural Compounds
- Photosynthetic Processes and Mechanisms
ProterixBio (United States)
2024
Menlo Systems (Germany)
2010
Technical University of Munich
2009
Center for Integrated Protein Science Munich
2009
California Institute of Technology
2004-2007
Howard Hughes Medical Institute
2007
Max Planck Institute of Biochemistry
1994-2004
Max Planck Society
1997-2004
Universitat Politècnica de València
2001
University of Regensburg
1995-1996
The tailspike protein (TSP) of Salmonella typhimurium phage P22 is a part the apparatus by which attaches to bacterial host and hydrolyzes O antigen. It has served as model system for genetic biochemical analysis folding. x-ray structure shortened TSP (residues 109 666) was determined 2.0 angstrom resolution. Each subunit homotrimer contains large parallel β helix. interdigitation polypeptide chains at carboxyl termini important protrimer formation in folding pathway thermostability mature protein.
The O-antigenic repeating units of lipopolysaccharides from Salmonella serogroups A, B, and D1 serve as receptors for the phage P22 tailspike protein, which also has receptor destroying endoglycosidase (endorhamnosidase) activity, integrating functions both hemagglutinin neuraminidase in influenza virus. Crystal structures protein complex with oligosaccharides, comprising two typhimurium, enteritidis, typhi 253Ty were determined at 1.8 A resolution. active-site topology Asp-392, Asp-395,...
Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function viral replication as integral component of ribonucleoprotein complex, associating with RNA and polymerase within core. The multifunctional nature NP makes it attractive target for antiviral intervention, inhibitors targeting this protein have recently been reported. In a parallel effort, we discovered structurally similar series influenza show that they interfere NP-dependent processes...
Inhibitors of the class I phosphoinositide 3-kinase (PI3K) isoform PI3Kα have received substantial attention for their potential use in cancer therapy. Despite particular attraction targeting PI3Kα, achieving selectivity inhibition this has proved challenging. Herein we report discovery inhibitors that over other isoforms and all kinases tested. In GDC-0032 (3, taselisib), previously minimized PI3Kβ relative to insoforms. Subsequently, extended our efforts identify PI3Kα-specific using...
Abstract With the ever-increasing number of synthesis-on-demand compounds for drug lead discovery, there is a great need efficient search technologies. We present successful application virtual screening method that combines two advances: (1) it avoids full library enumeration (2) products are evaluated by molecular docking, leveraging protein structural information. Crucially, these advances enable structure-based technique can efficiently explore libraries with billions molecules and...
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...
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite progress, improvements ADC index are desired. Peptide-based linkers that cleaved lysosomal proteases shown sufficient stability serum effective payload-release targeted cells. If linker can be preferentially hydrolyzed tumor-specific proteases, safety margin may improve. However, use of peptide-based limits our ability to...
ABSTRACT New approaches to antimicrobial drug discovery are urgently needed combat intractable infections caused by multidrug-resistant (MDR) bacteria. M ultiple v irulence f actor r egulator (MvfR or PqsR), a Pseudomonas aeruginosa quorum sensing transcription factor, regulates functions important in both acute and persistent infections. Recently identified non-ligand-based benzamine-benzimidazole (BB) inhibitors of MvfR suppress P. mice without perturbing bacterial growth. Here, we...
A prevalent observation in high-throughput screening and drug discovery programs is the inhibition of protein function by small-molecule compound aggregation. Here, we present X-ray structural description aggregation-based a protein–protein interaction involving tumor necrosis factor α (TNFα). An ordered conglomerate an aggregating inhibitor (JNJ525) induces quaternary structure switch TNFα that inhibits between receptors. SPD-304 may employ similar mechanism inhibition.
Human endogenous retroviruses (HERVs) comprise nearly 8% of the human genome and are derived from ancient integrations into germline. The biology HERVs is poorly defined, but there accumulating evidence supporting pathological roles in diverse diseases, such as cancer, autoimmune, neurodegenerative diseases. Functional proteins produced by HERV-encoded genes, including reverse transcriptases (RTs), which could be a contributor to pathology attributed aberrant HERV-K expression. To facilitate...
Abstract The transformation of 4-hydroxyphenylpyruvate to homogentisate, catalyzed by dioxygenase (HPPD), plays an important role in degrading aromatic amino acids. As the reaction product homogentisate serves as precursor for prenylquinone synthesis plants, enzyme is interesting target herbicides. In this study we report first x-ray structures plant HPPDs Zea mays and Arabidopsis their substrate-free form at 2.0 Å 3.0 resolution, respectively. Previous biochemical characterizations have...
We report here structure-guided optimization of a novel series NF-κB inducing kinase (NIK) inhibitors. Starting from modestly potent, low molecular weight lead, activity was improved by designing type 11/2 binding mode that accessed back pocket past the methionine-471 gatekeeper. Divergent modes in NIK and PI3K were exploited to dampen inhibition while maintaining within these series. Potent compounds discovered selectively inhibit nuclear translocation NF-κB2 (p52/REL-B) but not canonical...
The lantibiotic-synthesizing flavoprotein EpiD catalyzes the oxidative decarboxylation of peptidylcysteines to peptidyl-aminoenethiols. sequence motif responsible for flavin coenzyme binding and enzyme activity is conserved in different proteins from all kingdoms life. Dfp eubacteria archaebacteria salt tolerance yeasts plants belong this new family flavoproteins. enzymatic function these was not known, but our experiments suggested that they catalyze a similar reaction like and/or may have...