A5063659458- Protein Structure and Dynamics
- Enzyme Structure and Function
- Advanced NMR Techniques and Applications
- NMR spectroscopy and applications
- Galectins and Cancer Biology
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Electron Spin Resonance Studies
- Molecular spectroscopy and chirality
- Mass Spectrometry Techniques and Applications
- Signaling Pathways in Disease
- Toxin Mechanisms and Immunotoxins
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Genetics, Bioinformatics, and Biomedical Research
- Spectroscopy and Quantum Chemical Studies
- Advanced MRI Techniques and Applications
- Alzheimer's disease research and treatments
- Various Chemistry Research Topics
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Macrophage Migration Inhibitory Factor
- Bacterial Genetics and Biotechnology
- RNA Research and Splicing
Lund University
2015-2024
SARomics Biostructures (Sweden)
2010
University of Liège
2010
École Polytechnique Fédérale de Lausanne
2008
University of Groningen
2008
École Polytechnique
2008
Centre National de la Recherche Scientifique
2008
Columbia University
1994-2007
Russian Academy of Sciences
2007
European Molecular Biology Laboratory
2007
Ribonuclease H is an endonuclease that hydrolyzes the RNA moiety of RNA–DNA duplex molecules.Escherichia coliribonuclease involved in DNA replication, and retroviral ribonuclease essential for reverse transcription viral genome. To characterize intramolcular dynamical properties ofE. H, spin-lattic relaxation rate constants, spin-spin constants steady state nuclear Overhauser effects the15N spins were measured by using proton-detected heteronuclear NMR spectroscopy. The data analyzed a...
Internal protein dynamics are intimately connected to enzymatic catalysis. However, enzyme motions linked substrate turnover remain largely unknown. We have studied of an during catalysis at atomic resolution using nuclear magnetic resonance relaxation methods. During catalytic action the cyclophilin A, we detect conformational fluctuations active site that occur on a time scale hundreds microseconds. The rates strongly correlate with microscopic turnover. present results, together available...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNMR order parameters and free energy: an analytical approach its application to cooperative calcium(2+) binding by calbindin D9kMikael Akke, Rafael Brueschweiler, Arthur G. Palmer IIICite this: J. Am. Chem. Soc. 1993, 115, 21, 9832–9833Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/ja00074a073https://doi.org/10.1021/ja00074a073research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTMonitoring Macromolecular Motions on Microsecond to Millisecond Time Scales by R1ρ−R1 Constant Relaxation NMR SpectroscopyMikael Akke and Arthur G. PalmerView Author Information Department of Biochemistry Molecular Biophysics Columbia University, 630 West 168th Street New York, York 10032 Cite this: J. Am. Chem. Soc. 1996, 118, 4, 911–912Publication Date (Web):January 31, 1996Publication History Received18 October 1995Published online31...
Rational drug design is predicated on knowledge of the three-dimensional structure protein−ligand complex and thermodynamics ligand binding. Despite fundamental importance both enthalpy entropy in driving binding, role conformational rarely addressed design. In this work, we have probed its relative contribution to free energy binding carbohydrate recognition domain galectin-3. Using a combination NMR spectroscopy, isothermal titration calorimetry, X-ray crystallography, characterized three...
The recognition of carbohydrates by proteins is a fundamental aspect communication within and between living cells. Understanding the molecular basis carbohydrate–protein interactions prerequisite for rational design synthetic ligands. Here we report high- to ultra-high-resolution crystal structures carbohydrate domain galectin-3 (Gal3C) in ligand-free state (1.08 Å at 100 K, 1.25 298 K) complex with lactose (0.86 Å) or glycerol (0.9 Å). These reveal striking similarities positions water...
Understanding the driving forces underlying molecular recognition is of fundamental importance in chemistry and biology. The challenge to unravel binding thermodynamics into separate contributions interpret these terms. Entropic free energy are particularly difficult assess this regard. Here we pinpoint determinants differences ligand affinity carbohydrate domain galectin-3, using a combination isothermal titration calorimetry, X-ray crystallography, NMR relaxation, dynamics simulations...
Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized evaluated as inhibitors of galectin-1 galectin-3. Systematic tuning the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to discovery exceptional affinities (Kd down 1–2 nM) in symmetrically substituted thiodigalactosides well unsurpassed combination high affinity 7.5 selectivity (46-fold) over for by carrying one trifluorphenyltriazole coumaryl moiety....
The temperature dependence of the backbone motions in Escherichia coli ribonuclease HI was studied on multiple time scales by 15N nuclear magnetic spin relaxation. Laboratory frame relaxation data at 285, 300, and 310 K were analyzed using model-free reduced spectral density approaches. order parameters used to define a characteristic for N−H bond vectors picosecond nanosecond scales. temperatures secondary structure elements, loops, C-terminus are ∼1000, ∼300, ∼170 K, respectively. observed...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBackbone dynamics of calcium-loaded calbindin D9k studied by two-dimensional proton-detected nitrogen-15 NMR spectroscopyJohan Koerdel, Nicholas J. Skelton, Mikael Akke, Arthur G. Palmer, III, and Walter ChazinCite this: Biochemistry 1992, 31, 20, 4856–4866Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1...
Kinetic anomalies in protein folding can result from changes of the kinetic ground states (D, I, and N), transition state, or both. The 102-residue U1A has a symmetrically curved chevron plot which seems to mainly state. At low concentrations denaturant state occurs early reaction, whereas at high concentration it moves close native structure. In this study we use movement follow continuously formation growth U1A's nucleus by phi analysis. Although structure is generally delocalized displays...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of ion binding on the backbone dynamics calbindin D9k determined by nitrogen-15 NMR relaxationMikael Akke, Nicholas J. Skelton, Johan Kordel, Arthur G. Palmer, III, and Walter ChazinCite this: Biochemistry 1993, 32, 37, 9832–9844Publication Date (Print):September 21, 1993Publication History Published online1 May 2002Published inissue 21 September...
Halogen bonding is increasingly utilized in efforts to achieve high affinity and selectivity of molecules designed bind proteins, making it paramount understand the relationship between structure, dynamics, thermodynamic driving forces. We present a detailed analysis addressing this problem using series protein-ligand complexes involving single halogen substitutions - F, Cl, Br, I nearly identical structures. Isothermal titration calorimetry reveals an favorable binding enthalpy from F that...
Calbindin D<sub>28k</sub> is a member of the calmodulin superfamily Ca<sup>2+</sup>-binding proteins and contains six EF-hands. The protein generally believed to function as Ca<sup>2+</sup> buffer, but studies presented in this work indicate that it may also act sensor. results show Mg<sup>2+</sup> binds same sites Ca<sup>2+</sup>with an association constant ∼1.4·10<sup>3</sup>m<sup>−1</sup> 0.15 m KCl. four high affinity calbindin bind non-sequential, parallel manner. In presence...
Abstract To investigate the contribution to protein stability of electrostatic interactions between charged surface residues, we have studied effect substituting three negatively solvent exposed residues with their side‐chain amide analogs in bovine calbindin D 9k —a small (M r 8,500) globular calmodulin superfamily. The free energy urea‐induced unfolding for wildtype and seven mutant proteins has been measured. increased towards relative wildtype. experimental results correlate reasonably...