Hartmut Oschkinat

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Hartmut Oschkinat
Hartmut Oschkinat group retreat 20171122.jpg
Oschkinat in 2016
Born (1957-02-28) 28 February 1957 (age 67)
NationalityGerman
CitizenshipGerman
Alma mater Goethe University Frankfurt
Awards Günther Laukien Prize
Scientific career
Institutions FMP Berlin
Free University of Berlin
Thesis Analysis of the conformation of Cyclosporin in solution using NMR-spectroscopy: development and use of new methods  (1986)
Doctoral advisor Horst Kessler
Website www.leibniz-fmp.de/research/structuralbiology/researchgroups/oschkinat/intro.html

Hartmut Oschkinat (born 28 February 1957) [1] is a German structural biologist and professor for chemistry at the Free University of Berlin. His research focuses on the study of biological systems with solid-state nuclear magnetic resonance.

Contents

He is a member of the Editorial Boards of the Journal of Biomolecular NMR and Structure . [2] [3]

Life and career

Oschkinat studied chemistry at the Johann-Wolfgang-Goethe University of Frankfurt. He received his doctoral degree in 1986 under the supervision of Horst Kessler with the title "Analysis of the conformation of Cyclosporin in solution using NMR-spectroscopy: development and use of new methods." in the field of nuclear magnetic resonance spectroscopy (NMR). After his work as a postdoctoral researcher with Geoffrey Bodenhausen at the University of Lausanne, Oschkinat moved to the Max Planck Institute of Biochemistry in Martinsried in 1987 as a post-doc in the Lab of Marius Clore and Angela Gronenborn. There, he was working with Marius Clore, Angela Gronenborn and the Nobel laureate Robert Huber. After his habilitation at the Technical University of Munich in 1992, Hartmut Oschkinat moved to the European Molecular Biology Laboratory in Heidelberg. Since 1998, he is the head of the department NMR-supported Structural Biology at the Leibniz-Institut für Molekulare Pharmakologie in Berlin. [4]

Research

At the beginning of his career, Oschkinat worked in the field of solution-state NMR, and made fundamental contributions [5] to establish the role of multidimensional NMR spectroscopy in structural biology. After using solution-state NMR spectroscopy to determine three-dimensional structures of soluble proteins such as the pleckstrin homology domain [6] and the WW domain, [7] characterise protein–protein interactions involving the latter, [8] with applications in fragment-based drug discovery, [9] [10] he moved on to focus on the investigation of biological systems by solid-state NMR (ssNMR) with magic angle spinning. His group was the first to solve a protein structure using ssNMR; [11] the structure solved was that of a microcrystalline preparation of a SH3 domain. [12] Since 2005, his research group investigates complex biomolecular systems such as membrane proteins within the native lipid environment, [13] [14] [15] amyloid fibrils, [16] and oligomers. [17] Moreover, he develops methods to address challenging questions in structural biology where ssNMR can be applied with particular advantages, and have made particular contributions to the development of dynamic nuclear polarisation [18] [19] and proton detection using fast magic angle spinning. [20]

Notable Achievements

Related Research Articles

<span class="mw-page-title-main">Structural biology</span> Study of molecular structures in biology

Structural biology, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization.

<span class="mw-page-title-main">Chemical structure</span> Organized way in which molecules are ordered and sorted

A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together and can be represented using structural formulae and by molecular models; complete electronic structure descriptions include specifying the occupation of a molecule's molecular orbitals. Structure determination can be applied to a range of targets from very simple molecules to very complex ones.

<span class="mw-page-title-main">Nuclear magnetic resonance spectroscopy</span> Laboratory technique

Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic field. This re-orientation occurs with absorption of electromagnetic radiation in the radio frequency region from roughly 4 to 900 MHz, which depends on the isotopic nature of the nucleus and increased proportionally to the strength of the external magnetic field. Notably, the resonance frequency of each NMR-active nucleus depends on its chemical environment. As a result, NMR spectra provide information about individual functional groups present in the sample, as well as about connections between nearby nuclei in the same molecule. As the NMR spectra are unique or highly characteristic to individual compounds and functional groups, NMR spectroscopy is one of the most important methods to identify molecular structures, particularly of organic compounds.

<span class="mw-page-title-main">Solid-state nuclear magnetic resonance</span>

Solid-state NMR (ssNMR) spectroscopy is a technique for characterizing atomic level structure in solid materials e.g. powders, single crystals and amorphous samples and tissues using nuclear magnetic resonance (NMR) spectroscopy. The anisotropic part of many spin interactions are present in solid-state NMR, unlike in solution-state NMR where rapid tumbling motion averages out many of the spin interactions. As a result, solid-state NMR spectra are characterised by larger linewidths than in solution state NMR, which can be utilized to give quantitative information on the molecular structure, conformation and dynamics of the material. Solid-state NMR is often combined with magic angle spinning to remove anisotropic interactions and improve the resolution as well as the sensitivity of the technique.

Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

<span class="mw-page-title-main">Residual dipolar coupling</span>

The residual dipolar coupling between two spins in a molecule occurs if the molecules in solution exhibit a partial alignment leading to an incomplete averaging of spatially anisotropic dipolar couplings.

<span class="mw-page-title-main">Nuclear magnetic resonance</span> Spectroscopic technique based on change of nuclear spin state

Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field and respond by producing an electromagnetic signal with a frequency characteristic of the magnetic field at the nucleus. This process occurs near resonance, when the oscillation frequency matches the intrinsic frequency of the nuclei, which depends on the strength of the static magnetic field, the chemical environment, and the magnetic properties of the isotope involved; in practical applications with static magnetic fields up to ca. 20 tesla, the frequency is similar to VHF and UHF television broadcasts (60–1000 MHz). NMR results from specific magnetic properties of certain atomic nuclei. High-resolution nuclear magnetic resonance spectroscopy is widely used to determine the structure of organic molecules in solution and study molecular physics and crystals as well as non-crystalline materials. NMR is also routinely used in advanced medical imaging techniques, such as in magnetic resonance imaging (MRI). The original application of NMR to condensed matter physics is nowadays mostly devoted to strongly correlated electron systems. It reveals large many-body couplings by fast broadband detection and should not be confused with solid state NMR, which aims at removing the effect of the same couplings by Magic Angle Spinning techniques.

Nuclear magnetic resonance crystallography is a method which utilizes primarily NMR spectroscopy to determine the structure of solid materials on the atomic scale. Thus, solid-state NMR spectroscopy would be used primarily, possibly supplemented by quantum chemistry calculations, powder diffraction etc. If suitable crystals can be grown, any crystallographic method would generally be preferred to determine the crystal structure comprising in case of organic compounds the molecular structures and molecular packing. The main interest in NMR crystallography is in microcrystalline materials which are amenable to this method but not to X-ray, neutron and electron diffraction. This is largely because interactions of comparably short range are measured in NMR crystallography.

Nucleic acid NMR is the use of nuclear magnetic resonance spectroscopy to obtain information about the structure and dynamics of nucleic acid molecules, such as DNA or RNA. It is useful for molecules of up to 100 nucleotides, and as of 2003, nearly half of all known RNA structures had been determined by NMR spectroscopy.

Robert Guy Griffin is a Professor of Chemistry and director of the Francis Bitter Magnet Laboratory at Massachusetts Institute of Technology (MIT). He is known for his work in nuclear magnetic resonance (NMR) and developing high-field dynamic nuclear polarisation (DNP) for the study of biological solids. He has contributed many different methods and approaches now widely used in solid-state NMR spectroscopy, in particular in context of magic-angle-spinning NMR. For example, this extends to methods for resolution enhancement via heteronuclear decoupling, as well as techniques for polarisation transfer between nuclei.

Triple resonance experiments are a set of multi-dimensional nuclear magnetic resonance spectroscopy (NMR) experiments that link three types of atomic nuclei, most typically consisting of 1H, 15N and 13C. These experiments are often used to assign specific resonance signals to specific atoms in an isotopically-enriched protein. The technique was first described in papers by Ad Bax, Mitsuhiko Ikura and Lewis Kay in 1990, and further experiments were then added to the suite of experiments. Many of these experiments have since become the standard set of experiments used for sequential assignment of NMR resonances in the determination of protein structure by NMR. They are now an integral part of solution NMR study of proteins, and they may also be used in solid-state NMR.

Protein chemical shift prediction is a branch of biomolecular nuclear magnetic resonance spectroscopy that aims to accurately calculate protein chemical shifts from protein coordinates. Protein chemical shift prediction was first attempted in the late 1960s using semi-empirical methods applied to protein structures solved by X-ray crystallography. Since that time protein chemical shift prediction has evolved to employ much more sophisticated approaches including quantum mechanics, machine learning and empirically derived chemical shift hypersurfaces. The most recently developed methods exhibit remarkable precision and accuracy.

<span class="mw-page-title-main">Leibniz-Forschungsinstitut für Molekulare Pharmakologie</span>

The Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) is a research institute in the Leibniz Association, focussing on proteins as basic structures of cellular organisms. It is one of the large number of research institutions based in Berlin. The institute is situated on a research campus in Buch, a northern district of Berlin. Legally, the FMP and seven other Leibniz Institutes based in Berlin are represented by the Forschungsverbund Berlin .

<span class="mw-page-title-main">G. Marius Clore</span> Molecular biophysicist, structural biologist

G. Marius Clore MAE, FRSC, FMedSci, FRS is a British-born, Anglo-American molecular biophysicist and structural biologist. He was born in London, U.K. and is a dual U.S./U.K. Citizen. He is a Member of the National Academy of Sciences, a Fellow of the Royal Society, a Fellow of the Academy of Medical Sciences, a Fellow of the American Academy of Arts and Sciences, a NIH Distinguished Investigator, and the Chief of the Molecular and Structural Biophysics Section in the Laboratory of Chemical Physics of the National Institute of Diabetes and Digestive and Kidney Diseases at the U.S. National Institutes of Health. He is known for his foundational work in three-dimensional protein and nucleic acid structure determination by biomolecular NMR spectroscopy, for advancing experimental approaches to the study of large macromolecules and their complexes by NMR, and for developing NMR-based methods to study rare conformational states in protein-nucleic acid and protein-protein recognition. Clore's discovery of previously undetectable, functionally significant, rare transient states of macromolecules has yielded fundamental new insights into the mechanisms of important biological processes, and in particular the significance of weak interactions and the mechanisms whereby the opposing constraints of speed and specificity are optimized. Further, Clore's work opens up a new era of pharmacology and drug design as it is now possible to target structures and conformations that have been heretofore unseen.

<span class="mw-page-title-main">Lyndon Emsley</span> British chemist

David Lyndon Emsley FRSC is a British chemist specialising in solid-state nuclear magnetic resonance and a professor at EPFL. He was awarded the 2012 Grand Prix Charles-Leopold Mayer of the French Académie des Sciences and the 2015 Bourke Award of the Royal Society of Chemistry.

Marc Baldus is a physicist and professor of NMR spectroscopy at Utrecht University. He is especially known for his work in the field of structural biology using solid-state nuclear magnetic resonance (ssNMR) spectroscopy. He applies ssNMR methods to establish structure-function relationships in complex biomolecular systems including membrane and Amyloid proteins. In addition, he develops cellular NMR methods to study large molecular transport and insertion systems in bacteria as well as signal transduction mechanisms in eukaryotic cells.

Structural chemistry is a part of chemistry and deals with spatial structures of molecules and solids. For structure elucidation a range of different methods is used. One has to distinguish between methods that elucidate solely the connectivity between atoms (constitution) and such that provide precise three dimensional information such as atom coordinates, bond lengths and angles and torsional angles.

<span class="mw-page-title-main">Gerhard Wagner (physicist)</span> German-American physicist

Gerhard Wagner is a German-American physicist. Currently the Elkan Rogers Blout Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School, he is an Elected Fellow of the American Association for the Advancement of Science, German National Academy of Sciences Leopoldina, American Academy of Arts and Sciences, National Academy of Sciences and International Society of Magnetic Resonance.

<span class="mw-page-title-main">Mei Hong (chemist)</span> Chinese-American chemist

Mei Hong is a Chinese-American biophysical chemist and professor of chemistry at the Massachusetts Institute of Technology. She is known for her creative development and application of solid-state nuclear magnetic resonance (ssNMR) spectroscopy to elucidate the structures and mechanisms of membrane proteins, plant cell walls, and amyloid proteins. She has received a number of recognitions for her work, including the American Chemical Society Nakanishi Prize in 2021, Günther Laukien Prize in 2014, the Protein Society Young Investigator award in 2012, and the American Chemical Society’s Pure Chemistry award in 2003.

The Cluster of Excellence Frankfurt "Macromolecular Complexes" (CEF) was established in 2006 by Goethe University Frankfurt together with the Max Planck Institute of Biophysics and the Max Planck Institute for Brain Research in the context of the German Universities Excellence Initiative. Funding by the Deutsche Forschungsgemeinschaft (DFG) endet in October 2019. CEF grew out of the long-standing collaborative research on membrane proteins and RNA molecules and strengthened research efforts in these fields by recruiting further scientists to Frankfurt/Main. CEF brought together the research activities of up to 45 research groups, the majority of which were based on Riedberg Campus in Frankfurt/Main. CEF founded the Buchmann Institute for Molecular Life Sciences (BMLS).

References

  1. ↑ "Symposium: Biological Solid-State NMR and Beyond, in honour of Hartmut Oschkinat's 60th birthday". Leibniz-Institut für Molekulare Pharmakologie. Archived from the original (jpg) on 27 February 2017. Retrieved 24 January 2017.
  2. ↑ "Editorial Board of Journal of Biomolecular NMR" . Retrieved 2017-02-14.
  3. ↑ "Staff and Editorial Board of Structure" . Retrieved 2017-02-14.
  4. ↑ "Department of NMR-Supported Structural biology (Hartmut Oschkinat)". FMP Berlin. Archived from the original on 27 February 2017. Retrieved 25 January 2017.
  5. ↑ Oschkinat H, Griesinger C, Kraulis PJ, Sørensen OW, Ernst RR, Gronenborn AM, Clore GM (1988). "Three-dimensional NMR spectroscopy of a protein in solution". Nature. 332 (6162): 374–6. Bibcode:1988Natur.332..374O. doi:10.1038/332374a0. PMID   3352736. S2CID   4261068.
  6. ↑ Macias MJ, Musacchio A, Ponstingl H, Nilges M, Saraste M, Oschkinat H (1994). "Structure of the pleckstrin homology domain from beta-spectrin". Nature. 369 (6482): 675–7. Bibcode:1994Natur.369..675M. doi:10.1038/369675a0. PMID   8208297. S2CID   4358947.
  7. ↑ Macias MJ, Gervais V, Civera C, Oschkinat H (2000). "Structural analysis of WW domains and design of a WW prototype". Nat. Struct. Biol. 7 (5): 375–9. doi:10.1038/75144. PMID   10802733. S2CID   1328841.
  8. ↑ Macias MJ, Hyvönen M, Baraldi E, Schultz J, Sudol M, Saraste M, Oschkinat H (1996). "Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide". Nature. 382 (6592): 646–9. Bibcode:1996Natur.382..646M. doi:10.1038/382646a0. PMID   8757138. S2CID   4306964.
  9. ↑ Joshi M, Vargas C, Boisguerin P, Diehl A, Krause G, Schmieder P, Moelling K, Hagen V, Schade M, Oschkinat H (2006). "Discovery of low-molecular-weight ligands for the AF6 PDZ domain". Angew. Chem. Int. Ed. Engl. 45 (23): 3790–5. doi:10.1002/anie.200503965. PMID   16671149.
  10. ↑ Pellecchia M, Bertini I, Cowburn D, Dalvit C, Giralt E, Jahnke W, James TL, Homans SW, Kessler H, Luchinat C, Meyer B, Oschkinat H, Peng J, Schwalbe H, Siegal G (2008). "Perspectives on NMR in drug discovery: a technique comes of age". Nat Rev Drug Discov. 7 (9): 738–45. doi:10.1038/nrd2606. PMC   2891904 . PMID   19172689.
  11. ↑ Comellas G, Rienstra CM (2013). "Protein structure determination by magic-angle spinning solid-state NMR, and insights into the formation, structure, and stability of amyloid fibrils". Annu Rev Biophys. 42: 515–36. doi:10.1146/annurev-biophys-083012-130356. PMID   23527778.
  12. ↑ Castellani F, van Rossum B, Diehl A, Schubert M, Rehbein K, Oschkinat H (2002). "Structure of a protein determined by solid-state magic-angle-spinning NMR spectroscopy". Nature. 420 (6911): 98–102. Bibcode:2002Natur.420...98C. doi:10.1038/nature01070. PMID   12422222. S2CID   4422584.
  13. ↑ Hiller M, Krabben L, Vinothkumar KR, Castellani F, van Rossum BJ, Kühlbrandt W, Oschkinat H (2005). "Solid-state magic-angle spinning NMR of outer-membrane protein G from Escherichia coli". ChemBioChem. 6 (9): 1679–84. doi:10.1002/cbic.200500132. PMID   16138308. S2CID   39312280.
  14. ↑ Krabben L, van Rossum BJ, Jehle S, Bocharov E, Lyukmanova EN, Schulga AA, Arseniev A, Hucho F, Oschkinat H (2009). "Loop 3 of short neurotoxin II is an additional interaction site with membrane-bound nicotinic acetylcholine receptor as detected by solid-state NMR spectroscopy". J. Mol. Biol. 390 (4): 662–71. doi:10.1016/j.jmb.2009.05.016. PMID   19447114.
  15. ↑ Shahid SA, Bardiaux B, Franks WT, Krabben L, Habeck M, van Rossum BJ, Linke D (2012). "Membrane-protein structure determination by solid-state NMR spectroscopy of microcrystals". Nat. Methods. 9 (12): 1212–7. doi:10.1038/nmeth.2248. PMID   23142870. S2CID   5089257.[ permanent dead link ]
  16. ↑ Ferguson N, Becker J, Tidow H, Tremmel S, Sharpe TD, Krause G, Flinders J, Petrovich M, Berriman J, Oschkinat H, Fersht AR (2006). "General structural motifs of amyloid protofilaments". Proc. Natl. Acad. Sci. U.S.A. 103 (44): 16248–53. Bibcode:2006PNAS..10316248F. doi: 10.1073/pnas.0607815103 . PMC   1637568 . PMID   17060612.
  17. ↑ Jehle S, Rajagopal P, Bardiaux B, Markovic S, Kühne R, Stout JR, Higman VA, Klevit RE, van Rossum BJ, Oschkinat H (2010). "Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers". Nat. Struct. Mol. Biol. 17 (9): 1037–42. doi:10.1038/nsmb.1891. PMC   2957905 . PMID   20802487.
  18. ↑ Geiger MA, Orwick-Rydmark M, Märker K, Franks WT, Akhmetzyanov D, Stöppler D, Zinke M, Specker E, Nazaré M, Diehl A, van Rossum BJ, Aussenac F, Prisner T, Akbey Ü, Oschkinat H (2016). "Temperature dependence of cross-effect dynamic nuclear polarization in rotating solids: advantages of elevated temperatures". Phys Chem Chem Phys. 18 (44): 30696–30704. Bibcode:2016PCCP...1830696G. doi:10.1039/c6cp06154k. PMID   27791210.
  19. ↑ Stöppler D, Song C, van Rossum BJ, Geiger MA, Lang C, Mroginski MA, Jagtap AP, Sigurdsson ST, Matysik J, Hughes J, Oschkinat H (2016). "Dynamic Nuclear Polarization Provides New Insights into Chromophore Structure in Phytochrome Photoreceptors". Angew. Chem. Int. Ed. Engl. 55 (52): 16017–16020. doi:10.1002/anie.201608119. PMID   27879035.
  20. ↑ Nieuwkoop AJ, Franks WT, Rehbein K, Diehl A, Akbey Ü, Engelke F, Emsley L, Pintacuda G, Oschkinat H (2015). "Sensitivity and resolution of proton detected spectra of a deuterated protein at 40 and 60 kHz magic-angle-spinning". J. Biomol. NMR. 61 (2): 161–71. doi:10.1007/s10858-015-9904-0. PMID   25663049. S2CID   27308791.
  21. ↑ "Find people in the EMBO Communities". EMBO. Retrieved 24 January 2017.
  22. ↑ "Professor Walter Rosenthal New Scientific Director of the Max Delbrück Center". Health Capital Berlin Brandenburg. 6 January 2009. Retrieved 24 January 2017. Professor Hartmut Oschkinat shall hold the office of Acting Director of the FMP until a successor has been appointed.[ permanent dead link ]
  23. ↑ "Volker Haucke ist neuer Direktor des FMP". Forshungsverbund Berlin e.V. 9 January 2012. Archived from the original on 28 February 2017. Retrieved 24 January 2017. ...sagt Prof. Hartmut Oschkinat, der das Institut in den letzten drei Jahren kommissarisch leitete.
  24. ↑ "Scientific Evaluation". Central European Institute of Technology. June 2012. Archived from the original on 9 June 2017. Retrieved 24 January 2017.
  25. ↑ "CEITEC - Step Forward in Material and Life Sciences" (PDF). Technology Centre CAS. p. 13. Archived from the original (PDF) on 27 December 2019. Retrieved 24 January 2017.
  26. ↑ "NMRS Members". National Magnetic Resonance Society of India. Retrieved 27 February 2017.
  27. ↑ "Tutorial & Award Lectures". ENC conference. Archived from the original on 27 February 2017. Retrieved 24 January 2017.
  28. ↑ "2014 Laukien: Hartmut Oschkinat (Leibniz-Institut, Berlin)". Vimeo. 2015-11-12. Retrieved 24 January 2017.
  29. ↑ "Bruker: Laukien Prize was awarded to six solid-state NMR spectroscopists". Bruker. Archived from the original on 27 December 2019. Retrieved 24 January 2017.
  30. ↑ "Monday at ENC: Laukien Prize Winners 2014". The Resonance. 2014-03-25. Retrieved 24 January 2017.
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