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Dr. Heike M. Kropp Dr. Samra Ludmann Dr. Kay Diederichs Dr. Karin Betz Dr. Andreas Marx 《Chembiochem : a European journal of chemical biology》2021,22(21):3060-3066
With increasing temperature, nucleobases in DNA become increasingly damaged by hydrolysis of exocyclic amines. The most prominent damage includes the conversion of cytosine to uracil and adenine to hypoxanthine. These damages are mutagenic and put the integrity of the genome at risk if not repaired appropriately. Several archaea live at elevated temperatures and thus, are exposed to a higher risk of deamination. Earlier studies have shown that DNA polymerases of archaea have the property of sensing deaminated nucleobases in the DNA template and thereby stalling the DNA synthesis during DNA replication providing another layer of DNA damage recognition and repair. However, the structural basis of uracil and hypoxanthine sensing by archaeal B-family DNA polymerases is sparse. Here we report on three new crystal structures of the archaeal B-family DNA polymerase from Thermococcus kodakarensis (KOD) DNA polymerase in complex with primer and template strands that have extended single stranded DNA template 5’-overhangs. These overhangs contain either the canonical nucleobases as well as uracil or hypoxanthine, respectively, and provide unprecedented structural insights into their recognition by archaeal B-family DNA polymerases. 相似文献
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Felix Schmutzler Christopher Zschiesche Juliane Titus David Poppitz Jens Freiding Rainer Rakoczy Andreas Reitzmann Roger Gläser 《化学,工程师,技术》2021,93(6):981-989
The hydroisomerization of two long-chain n-alkane mixtures was investigated over bifunctional Pt/H-ZSM-5 catalysts before and after dealumination of preshaped zeolite/binder pellets. The hydroisomerization over the dealuminated catalysts leads to more isomers and less cracking products. Consequently, higher ratios of multi- to mono-branched isomerization products are formed as expected for large- rather than medium-pore zeolites. This indicates a higher availability of space in the vicinity of the active sites and provides an attractive route to make medium-pore zeolites suitable for upgrading higher boiling hydrocarbon feeds. 相似文献
5.
Dr. Barbara Wienen-Schmidt Matthias Oebbeke Dr. Khang Ngo Prof. Dr. Andreas Heine Prof. Dr. Gerhard Klebe 《ChemMedChem》2021,16(1):292-300
In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes. 相似文献
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Anna Kutschenko Selma Staege Karen Grütz Hannes Glaß Norman Kalmbach Thomas Gschwendtberger Lisa M. Henkel Johanne Heine Anne Grünewald Andreas Hermann Philip Seibler Florian Wegner 《International journal of molecular sciences》2021,22(7)
Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia. 相似文献
7.
Valentin G. Greb Martin Bertau Axel Düker Andreas Geisbauer Peter Fröhlich 《化学,工程师,技术》2021,93(11):1827-1832
Petrochemical catalysts are widely used in the industry. For the production of cumene, zeolite-based catalysts containing phosphoric acid are applied. Over the time, coking deactivates the surface, and the catalyst has to be exchanged and disposed of. Different process approaches for recycling the phosphoric acid-containing catalysts were investigated. Related preliminary investigations have shown that calcination of the used catalyst is necessary prior to reprocessing. By digesting the catalyst with hydrofluoric acid, ∼96 % phosphate was recovered. However, this process is very costly in terms of process technology. More promising is digestion by basic or acidic routes. Several options are possible here, and digestion with H3PO4 proved to be particularly suitable. Here, phosphate yields reached up to 98.8 %, with a positive balance of economic efficiency at the same time. The catalyst can be produced and recycled in the same plant with the same reagents, what constitutes a major breakthrough towards sustainability in industrial catalysis. 相似文献
8.
Anna Sib Tobias M. Milzarek Alexander Herrmann Dr. Lila Oubraham Jonas I. Müller Prof. Dr. Andreas Pichlmair Prof. Dr. Ruth Brack-Werner Prof. Dr. Tobias A. M. Gulder 《Chembiochem : a European journal of chemical biology》2020,21(4):492-495
Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family. 相似文献
9.
The corrosion resistance of aluminium surfaces is closely linked to the surface state after a grinding process. For years, iron-containing abrasive materials were suspected to lead to increased corrosion susceptibility after processing of aluminium surfaces. To prove a possible correlation between the iron content of an abrasive and the corrosion behaviour of aluminium components, scientific investigations and experimentally practical corrosion tests are necessary. For the current investigation, specimens of a technical Al-Si alloy from the same batch were used. The test specimens were mechanically ground with various resin-bonded model abrasives containing different iron contents. The performed corrosion tests did not reveal a negative influence of the different iron-containing abrasives on the corrosion behaviour of the Al–Si alloy. However, the most sensitive measuring method (electrochemical noise) showed differences in the surface activity depending on the type of abrasive. 相似文献
10.
Ina Eibl Daniela von der Haar Marius Jesdinszki Andreas Stäbler Markus Schmid Horst‐Christian Langowski 《应用聚合物科学杂志》2018,135(25)
In order to minimize the utilization of non‐renewable fossil resources, novel polymer sources for food packaging are being investigated. Micellar Lupin Protein (MLP), produced by dilution precipitation has great potential as functional laminating adhesive due to its high adhesion‐ and oxygen‐barrier properties. Formulations of MLP are used as laminating adhesive between high density‐polyethylene foil and paper as well as coating for poly(ethylene terephthalate) foil. The application of glycerol, sorbitol and combinations thereof as plasticizers are being investigated. Adhesive behavior as well as oxygen‐ and water vapor barrier properties were tested. The addition of both plasticizers enabled the preparation of processable coatings showing coherent and homogeneous morphology with improved adhesive behavior and oxygen barrier. When using sorbitol oxygen permeation coefficients of 0.93 cm3 (STP) 100 µm m?2 d?1 bar?1 were achieved. The laminates containing only sorbitol provided adhesion properties comparable to standard polyurethane laminates with cohesion failure in 100% of the by T‐Peel‐Test examined cases. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46383. 相似文献