TY - GEN A1 - Wolff, Martin A1 - Gast, Klaus A1 - Evers, Andreas A1 - Kurz, Michael A1 - Pfeiffer-Marek, Stefania A1 - Schüler, Anja A1 - Seckler, Robert A1 - Thalhammer, Anja T1 - A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4 T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1161 KW - biophysics KW - diabetes KW - peptides KW - oligomerization KW - conformational change KW - molecular modeling KW - static and dynamic light scattering KW - spectroscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-522081 SN - 1866-8372 IS - 9 ER - TY - JOUR A1 - Wolff, Martin A1 - Gast, Klaus A1 - Evers, Andreas A1 - Kurz, Michael A1 - Pfeiffer-Marek, Stefania A1 - Schüler, Anja A1 - Seckler, Robert A1 - Thalhammer, Anja T1 - A Conserved Hydrophobic Moiety and Helix-Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4 JF - Biomolecules N2 - Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers. KW - biophysics KW - diabetes KW - peptides KW - oligomerization KW - conformational change KW - molecular modeling KW - static and dynamic light scattering KW - spectroscopy Y1 - 2021 U6 - https://doi.org/10.3390/biom11091305 SN - 2218-273X VL - 11 IS - 9 PB - MDPI CY - Basel ER - TY - JOUR A1 - Peng, Lei A1 - Utesch, Tillmann A1 - Yarman, Aysu A1 - Jeoung, Jae-Hun A1 - Steinborn, Silke A1 - Dobbek, Holger A1 - Mroginski, Maria Andrea A1 - Tanne, Johannes A1 - Wollenberger, Ursula A1 - Scheller, Frieder W. T1 - Surface-Tuned Electron Transfer and Electrocatalysis of Hexameric Tyrosine-Coordinated Heme Protein JF - Chemistry - a European journal N2 - Molecular modeling, electrochemical methods, and quartz crystal microbalance were used to characterize immobilized hexameric tyrosine-coordinated heme protein (HTHP) on bare carbon or on gold electrodes modified with positively and negatively charged self-assembled monolayers (SAMs), respectively. HTHP binds to the positively charged surface but no direct electron transfer (DET) is found due to the long distance of the active sites from the electrode surfaces. At carboxyl-terminated surfaces, the neutrally charged bottom of HTHP can bind to the SAM. For this "disc" orientation all six hemes are close to the electrode and their direct electron transfer should be efficient. HTHP on all negatively charged SAMs showed a quasi-reversible redox behavior with rate constant k(s) values between 0.93 and 2.86 s(-1) and apparent formal potentials E-app(0)' between -131.1 and -249.1 mV. On the MUA/MU-modified electrode, the maximum surface concentration corresponds to a complete monolayer of the hexameric HTHP in the disc orientation. HTHP electrostatically immobilized on negatively charged SAMs shows electrocatalysis of peroxide reduction and enzymatic oxidation of NADH. KW - electrochemistry KW - electron transfer KW - heme proteins KW - molecular modeling KW - monolayers Y1 - 2015 U6 - https://doi.org/10.1002/chem.201405932 SN - 0947-6539 SN - 1521-3765 VL - 21 IS - 20 SP - 7596 EP - 7602 PB - Wiley-VCH CY - Weinheim ER - TY - THES A1 - Götze, Jan Philipp T1 - Influence of protein and solvent environments on quantum chemical properties of photosynthesis enzymes and photoreceptors T1 - Einfluss von Protein- und Lösungsmittelumgebungen auf quantenchemische Eigenschaften von Photosynthese-Enzymen und -Photorezeptoren N2 - This thesis contains quantum chemical models and force field calculations for the RuBisCO isotope effect, the spectral characteristics of the blue-light sensor BLUF and the light harvesting complex II. The work focuses on the influence of the environment on the corresponding systems. For RuBisCO, it was found that the isotopic effect is almost unaffected by the environment. In case of the BLUF domain, an amino acid was found to be important for the UV/vis spectrum, but unaccounted for in experiments so far (Ser41). The residue was shown to be highly mobile and with a systematic influence on the spectral shift of the BLUF domain chromophore (flavin). Finally, for LHCII it was found that small changes in the geometry of a Chlorophyll b/Violaxanthin chromophore pair can have strong influences regarding the light harvesting mechanism. Especially here it was seen that the proper description of the environment can be critical. In conclusion, the environment was observed to be of often unexpected importance for the molecular properties, and it seems not possible to give a reliable estimate on the changes created by the presence of the environment. N2 - Diese Arbeit beinhaltet quantenchemische und molekularmechanische Modelle zum Isotopeneffekt des Enzyms RuBisCO, der spektralen Charakterisierung des Blaulicht-Rezeptors BLUF und dem Lichtsammelkomplex II (LHCII). Es wurden vor allem die Einflüsse der Umgebung auf die entsprechenden Systeme untersucht. Für RuBisCO wurde gefunden, dass der Isotopeneffekt nur marginal von der Umgebung abhängt. Im Falle der BLUF Domäne wurde eine Aminosäure charakterisiert (Ser41), die bis dato experimentell noch nicht beschrieben war. Es wurde festgestellt, dass Ser41 hochmobil ist und einen systematischen Einfluss auf die spektrale Verschiebung des BLUF Chromophors (Flavin) hat. Schließlich wurde bei LHCII festgestellt, dass kleine Veränderungen in der Geometrie eines Chlorophyll b/Violaxanthin Chromophorenpaares bereits massive Einflüsse auf den Mechanismus des Lichtsammelprozesses haben können. Insbesondere hier zeigt sich, wie kritisch die genaue Beschreibung der Umgebung ist. Zusammenfassend wurde beobachtet, dass sich die Umgebung in oft unerwarteter Weise auf die molekularen Eigenschaften auswirken kann und es daher nicht möglich zu sein scheint, die entsprechenden Effekte vorher abzuschätzen. KW - Photosynthese KW - Molekülmodelle KW - RuBisCO KW - LHCII KW - Blaulichtsensoren KW - Photosynthesis KW - molecular modeling KW - RuBisCO KW - LHCII KW - Blue-light sensors Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-51135 ER -