Research Area A - Publications 2015
Quantum Yield of Cyclobutane Pyrimidine Dimer Formation Via the Triplet Channel Determined by Photosensitization
J. Phys. Chem. B, 2016, 120 (2), pp 292–298, DOI: 10.1021/acs.jpcb.5b08568
J. Phys. Chem, online article
UV-induced formation of the cyclobutane pyrimidine dimer (CPD) lesion is investigated by stationary and time-resolved photosensitization experiments. The photosensitizer 2′-methoxyacetophenone with high intersystem crossing efficiency and large absorption cross-section in the UV-A range was used. A diffusion controlled reaction model is presented. Time-resolved ...
J. Am. Chem. Soc., DOI: 10.1021/jacs.5b09753
Absorption of UV-radiation in nucleotides initiates a number of photophysical and photochemical processes, which may finally cause DNA damage. One major decay channel of photoexcited DNA leads to reactive charge transfer states. This study shows that these states trigger self-repair of DNA photolesions. The experiments were performed by UV spectroscopy and HPLC ...
Chem. Commun.,52, 1254-1257, DOI: 10.1039/C5CC08884D
We have shown previously that carbohydrate-specific bacterial adhesion to a non-physiological surface can be photocontrolled by reversible E/Z isomerisation using azobenzene-functionalised sugars. Here, this approach is applied to the surface of human cells. We show not only that bacterial adhesion to the azobenzene glycoside-modified cell surface is higher in ...
Journal of Molecular Biology, Volume 427, Issue 22, Pages 3572–3586, doi:10.1016/j.jmb.2015.09.012
The association of light chains (LCs) and heavy chains is the basis for functional antibodies that are essential for adaptive immune responses. However, in some cases, LCs and especially fragments consisting of the LC variable (VL) domain are pathologically deposited in fatal aggregation diseases. The two domains of the LC are connected by a highly conserved ...
Nature Nanotechnology, doi:10.1038/nnano.2015.231
Strep-Tactin, an engineered form of streptavidin, binds avidly to the genetically encoded peptide Strep-tag II in a manner comparable to streptavidin binding to biotin. These interactions have been used in protein purification and detection applications. However, in single-molecule studies, for example using atomic force microscopy-based single-molecule force ...
Nature Communications 6, Article number: 8508 doi:10.1038/ncomms9508
Hydrogen evolution from photocatalytic reduction of water holds promise as a sustainable source of carbon-free energy. Covalent organic frameworks (COFs) present an interesting new class of photoactive materials, which combine three key features relevant to the photocatalytic process, namely crystallinity, porosity and tunability. Here we synthesize a series of ...
ChemPhysChem ,16, 3483 – 3487, DOI: 10.1002/cphc.201500582
Stationary and time-resolved experiments show that 2′-methoxyacetophenone (2-M) is an interesting compound for the investigation of triplet states in thymine samples. Time-resolved emission experiments show that the fluorescence lifetime of 2-M is 660 ps. A similar time constant of 680 ps is found in transient IR experiments. The data indicate efficient ...
Structural, Biochemical, and Computational Studies Reveal the Mechanism of Selective Aldehyde Dehydrogenase 1A1 Inhibition by Cytotoxic Duocarmycin Analogues
Angew. Chem. Int. Ed., Volume 127, Issue 46, Pages 13754–13758, DOI: 10.1002/anie.201505749
Analogues of the natural product duocarmycin bearing an indole moiety were shown to bind aldehyde dehydrogenase 1A1 (ALDH1A1) in addition to DNA, while derivatives without the indole solely addressed the ALDH1A1 protein. The molecular mechanism of selective ALDH1A1 inhibition by duocarmycin analogues was unraveled through cocrystallization, mutational studies, ...
ChemBioChem, 2015, Volume 16, Issue 14, pages 2023–2028, DOI: 10.1002/cbic.201500361
ChemBioChem, online article
The effect of galectin-mediated microdomain formation on the spatiotemporal dynamics of glycosylated membrane proteins in human microvascular endothelial cells (HMEC-1) was studied qualitatively and quantitatively by high-resolution fluorescence microscopy and artificially mimicked by metabolic glycoprotein engineering. Two types of membrane proteins, sialic ...
Nucleotides regulate the mechanical hierarchy between subdomains of the nucleotide binding domain of the Hsp70 chaperone DnaK
PNAS, vol. 112, no. 33, 10389–10394, doi: 10.1073/pnas.1504625112
PNAS, online article
The regulation of protein function through ligand-induced conformational changes is crucial for many signal transduction processes. The binding of a ligand alters the delicate energy balance within the protein structure, eventually leading to such conformational changes. In this study, we elucidate the energetic and mechanical changes within the subdomains of the ...
J. Cell Biol., Vol. 210 No. 4, 629–646, www.jcb.org/cgi/doi/10.1083/jcb.201504006
J. Cell Biol., online article
Assembly of the Gag polyprotein into new viral particles in infected cells is a crucial step in the retroviral replication cycle. Currently, little is known about the onset of assembly in the cytosol. In this paper, we analyzed the cytosolic HIV-1 Gag fraction in real time in live cells using advanced fluctuation imaging methods and thereby provide detailed ...
Importance of dipole moments and ambient polarity for the conformation of Xaa–Pro moieties – a combined experimental and theoretical study
Chem. Sci., 6, 6725-6730, DOI: 10.1039/C5SC02211H
Chem. Sci., online article
NMR spectroscopic studies with a series of proline derivatives revealed that the polarity of the environment has a significant effect on the trans:cis isomer ratio of Xaa–Pro bonds. Computational studies showed that this effect is due to differences in the overall dipole moments of trans and cis conformers. Comparisons between the conformational properties of ...
Nano Lett., 2015, 15 (11), pp 7370–7376, DOI: 10.1021/acs.nanolett.5b02727
Here we employ single-molecule force spectroscopy with an atomic force microscope (AFM) and steered molecular dynamics (SMD) simulations to reveal force propagation pathways through a mechanically ultrastable multidomain cellulosome protein complex. We demonstrate a new combination of network-based correlation analysis supported by AFM directional pulling ...
JACS, online article
Human DNA glycosylase, hOGG1, is known to perform DNA repair by cleaving oxidized guanine (8OG) from the DNA. Despite numerous experimental and theoretical investigations, the underlying selective molecular mechanism has remained a mystery. Here we present a mechanism that explains how hOGG1’s catalytic pocket is able to host an undamaged guanine base, but is not ...
Kinetic and Theoretical Studies of Beta-Lactone Reactivity—A Quantitative Scale for Biological Application
ChemPlusChem, Volume 80, Issue 11, pages 1673–1679, DOI: 10.1002/cplu.201500246
Natural products comprise a rich source for bioactive molecules with medicinal relevance. Many of these contain electrophilic scaffolds that bind conserved enzyme active sites covalently. Prominent examples include beta-lactams and beta-lactones, which specifically acylate serine residues in diverse peptidases. Although these scaffolds appear similar, their ...
Structure, Volume 23, Issue 8, p1507–1515, DOI: http://dx.doi.org/10.1016/j.str.2015.05.021
Peptide-protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. Here, we present a new fully blind flexible peptide-protein docking protocol, pepATTRACT, which ...
J. Phys. Chem. B, 2015, DOI: 10.1021/acs.jpcb.5b04694, 119 (28), pp 8685–8692 published on 23.06.2015
J. Phys. Chem. B, online article
UV-induced Dewar lesion formation is investigated in single- and double-stranded oligonucleotides with ultrafast vibrational spectroscopy. The quantum yield for the conversion of the (6–4) lesion to the Dewar isomer in DNA strands is reduced by a factor of 4 in comparison to model dinucleotides. Time resolved spectroscopy reveals a fast process in the excited ...
Application of Enhanced Sampling Monte Carlo Methods for High-Resolution Protein-Protein Docking in Rosetta
PLOS ONE, DOI:10.1371/journal.pone.0125941
The high-resolution refinement of docked protein-protein complexes can provide valuable structural and mechanistic insight into protein complex formation complementing experiment. Monte Carlo (MC) based approaches are frequently applied to sample putative interaction geometries of proteins including also possible conformational changes of the binding partners. In ...
Anle138b and related compounds are aggregation specific fluorescence markers and reveal high affinity binding to α-synuclein aggregates
Biochimica et Biophysica Acta, online article
Background: Special diphenyl-pyrazole compounds and in particular anle138b were found to reduce the progression of prion and Parkinson's disease in animal models. The therapeutic impact of these compounds was attributed to the modulation of α-synuclein and prion-protein aggregation related to these diseases. Methods: Photophysical and photochemical properties of ...
THE JOURNAL OF BIOLOGICAL CHEMISTRY, VOL. 290, NO. 28, pp. 17250–17261, DOI 10.1074/jbc.M115.650309
THE JOURNAL OF BIOLOGICAL CHEMISTRY, online article
Members of the YidC/Oxa1/Alb3 protein family mediate membrane protein insertion and this process is initiated by the assembly of YidC:ribosome nascent chain (RNC) complexes at the inner leaflet of the lipid bilayer. The positively charged C-terminus of Escherichia coli YidC plays a significant role in ribosome binding but is not the sole determinant as deletion ...
Scientific Reports, online article
The ubiquitous occurrence of DNA damages renders its repair machinery a crucial requirement for the genomic stability and the survival of living organisms. Deficiencies in DNA repair can lead to carcinogenesis, Alzheimer, or Diabetes II, where increased amounts of oxidized DNA bases have been found in patients. Despite the highest mutation frequency among ...
ChemPhysChem , 16, 2085 – 2090, DOI: 10.1002/cphc.201500193
Increased thermal or mechanical stability of DNA duplexes is desired for many applications in nanotechnology or -medicine where DNA is used as a programmable building block. Modifications of pyrimidine bases are known to enhance thermal stability and have the advantage of standard base-pairing and easy integration during chemical DNA synthesis. Through ...
Deutsche Bunsen Gesellschaft
Am 14.05.2015 wurde CIPSM-Wissenschaftler Christoph Bräuchle im Rahmen der 114. Hauptversammlung der Deutschen Bunsen-Gesellschaft für Physikalische Chemie e.V. die Walther-Nernst-Denkmünze durch den Ersten Vorsitzenden der Deutschen Bunsengesellschaft, Herrn Prof. J. Sauer, überreicht. Dieser Preis wird nur alle drei Jahre verliehen an WissenschaftlerInnen, ...
Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery
Nanoscale, online article
A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core–shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform ...
Nature Communications, 2015, doi:10.1038/ncomms7655, 6, Article number: 6655 published on 08.04.2015
Nature Communications, online article
The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a dynamic, elongated protein that consists of a flexible N-terminal module, a long linker and a rigid C-terminal module. Binding ...
Science, online article
We demonstrate that discrete three-dimensional (3D) DNA components can specifically self-assemble in solution on the basis of shape-complementarity and without base pairing. Using this principle, we produced homo- and heteromultimeric objects, including micrometer-scale one- and two-stranded filaments and lattices, as well as reconfigurable devices, including an ...
Rev. Sci. Instrum., 86, 035109, http://dx.doi.org/10.1063/1.4915145
Since the atomic force microscope (AFM) has evolved into a general purpose platform for mechanical experiments at the nanoscale, the need for a simple and generally applicable localization of the AFM cantilever in the reference frame of an optical microscope has grown. Molecular manipulations like in single molecule cut and paste or force spectroscopy as well as ...
CIPSM is thrilled that CIPSM researcher Hendrik Dietz was awarded with the Gottfried Wilhelm Leibniz Price, the most prestigious German research award. Hendrik will receive 2,5 Mio. € for his work that he started 2009 here at CIPSM.
A reduced-scaling density matrix-based method for the computation of the vibrational Hessian matrix at the self-consistent field level
J. Chem. Phys., 142, 094101, http://dx.doi.org/10.1063/1.4908131
J. Chem. Phys., online article
An analytical method to calculate the molecular vibrational Hessian matrix at the self-consistent field level is presented. By analysis of the multipole expansions of the relevant derivatives of Coulomb-type two-electron integral contractions, we show that the effect of the perturbation on the electronic structure due to the displacement of nuclei decays at least ...
Rev. Sci. Instrum., online article
An exchange system is presented, which allows ultrafast experiments with high excitation rates (1 kHz) on samples with reaction cycles in the range of a few seconds and small sample volumes of about 0.3 ml. The exchange is accomplished using a commercially available cuvette by the combination of a special type of magnetic stirring with transverse translational ...
Preselective Screening for Linear-Scaling Exact Exchange-Gradient Calculations for Graphics Processing Units and General Strong-Scaling Massively Parallel Calculations
J. Chem. Theory Comput., online article
We present an extension of our recently presented PreLinK scheme ( J. Chem. Phys. 2013, 138, 134114) for the exact exchange contribution to nuclear forces. The significant contributions to the exchange gradient are determined by preselection based on accurate shell-pair contributions to the SCF exchange energy prior to the calculation. Therefore, our method is ...
J. Chem. Theory Comput, online article
Polytwistane is an intriguing hydrocarbon nanorod that has not been experimentally realized to date. To facilitate its identification in complex reaction mixtures, the 1H and 13C nuclear magnetic resonance (NMR) spectra of idealized polytwistane were calculated using two distinct quantum chemical approaches. In addition, the NMR spectra of related hydrocarbon ...
PLOS Pathogens, online article
The cellular endosomal sorting complex required for transport (ESCRT) machinery is involved in membrane budding processes, such as multivesicular biogenesis and cytokinesis. In HIV-infected cells, HIV-1 hijacks the ESCRT machinery to drive HIV release. Early in the HIV-1 assembly process, the ESCRT-I protein Tsg101 and the ESCRT-related protein ALIX are recruited ...
eLife 2015;4:e04599, DOI: http://dx.doi.org/10.7554/eLife.04599
eLife, online article
Actin filament dynamics govern many key physiological processes from cell motility to tissue morphogenesis. A central feature of actin dynamics is the capacity of filaments to polymerize and depolymerize at their ends in response to cellular conditions. It is currently thought that filament kinetics can be described by a single rate constant for each end. In this ...
Annual Review of Physical Chemistry, online article
Ultraviolet (UV) radiation is a leading external hazard to the integrity of DNA. Exposure to UV radiation triggers a cascade of chemical reactions, and many molecular products (photolesions) have been isolated that are potentially dangerous for the cellular system. The early steps that take place after UV absorption by DNA have been studied by ultrafast ...
Biophysical Journal, Volume 108, Issue 3, p678–686, http://dx.doi.org/10.1016/j.bpj.2014.11.3482
Many small proteins fold highly cooperatively in an all-or-none fashion and thus their native states are well protected from thermal fluctuations by an extensive network of interactions across the folded structure. Because protein structures are stabilized by local and nonlocal interactions among distal residues, dissecting individual substructures from the ...
Biophysical Journal, online article
Protein-protein docking programs can give valuable insights into the structure of protein complexes in the absence of an experimental complex structure. Web interfaces can facilitate the use of docking programs by structural biologists. Here, we present an easy web interface for protein-protein docking with the ATTRACT program. While aimed at nonexpert users, the ...
Chem. Commun., online article
The synthesis of novel, chignolin-derived peptides comprising the azobenzene photoswitch [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is reported. Reversible photoswitching behavior led to folding into β-hairpin-like structures, as unequivocally demonstrated by CD, FT-IR and NMR spectroscopy.