- Photosynthetic Processes and Mechanisms
- Light effects on plants
- Enzyme Structure and Function
- Drug Transport and Resistance Mechanisms
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Biocrusts and Microbial Ecology
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Photoreceptor and optogenetics research
- Glycosylation and Glycoproteins Research
- Microtubule and mitosis dynamics
- Plant and Biological Electrophysiology Studies
- Protein Structure and Dynamics
- Algal biology and biofuel production
- Genomics and Phylogenetic Studies
- Aldose Reductase and Taurine
- Lipid Membrane Structure and Behavior
- Molecular Biology Techniques and Applications
- Advanced Chemical Physics Studies
- Trace Elements in Health
- Spectroscopy and Quantum Chemical Studies
- Advanced Fluorescence Microscopy Techniques
- Veterinary medicine and infectious diseases
- 14-3-3 protein interactions
University of Gothenburg
2015-2025
University of Wisconsin–Milwaukee
2019
SPring-8
2019
University of Chicago
2019
Kyoto University
2019
Japan Synchrotron Radiation Research Institute
2019
Northeastern Illinois University
2019
Research Complex at Harwell
2017
Imperial College London
2017
Rutherford Appleton Laboratory
2017
Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation protein through structural changes. We present serial femtosecond X-ray crystallographic data chromophore-binding domains bacterial phytochrome at delay times 1 ps 10 after photoexcitation. The reveal twist D-ring, which partial detachment chromophore from protein. Unexpectedly, conserved so-called...
Many pathogenic bacteria utilise sialic acids as an energy source or use them external coating to evade immune detection. As such, that colonise sialylated environments deploy specific transporters mediate import of scavenged acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation SiaT, acid transporter from Proteus mirabilis. SiaT is secondary active the sodium solute symporter (SSS) family, which Na
Article1 September 2017Open Access Source DataTransparent process Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD Kiran Bountra Department of Life Sciences, Imperial College London, UK Rutherford Appleton Laboratory, Research Complex at Harwell, Oxfordshire, Search more papers this author Gregor Hagelueken Institute Physical and Theoretical Chemistry, University Bonn, Germany Hassanul G Choudhury Valentina Corradi Centre Molecular Simulation...
Whether long-range quantum coherent states could exist in biological systems, and beyond low-temperature regimes where physics is known to be applicable, has been the subject debate for decades. It was proposed by Fröhlich that vibrational modes within protein molecules can order condense into a lowest-frequency mode process similar Bose-Einstein condensation, thus macroscopic coherence potentially observed systems. Despite prediction of these so-called condensates almost five decades ago,...
LC8 dynein light chain (DYNLL) is a eukaryotic hub protein that thought to function as dimerization engine. Its interacting partners are involved in wide range of cellular functions. In its dozens hitherto identified binding DYNLL binds linear peptide segment. The known segments define loosely characterized motif: [D/S]-4K-3X-2[T/V/I]-1Q0[T/V]1[D/E]2. motifs localized disordered the DYNLL-binding proteins and often flanked by coiled coil or other potential domains. Based on directed...
Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known inhibit AKR1C3 a nonselective manner because of COX-off effects. Here we designed two analogues by proposing bioisosteric connection between the carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found selective manner. In particular, derivative highly...
Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli a response regulator through histidine kinase domain. Phytochromes switch between red light-absorbing and far-red states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable activity. Here, we resolve long-standing conundrum by comparatively analyzing interactions...
Abstract Phytochrome proteins detect red/far-red light to guide the growth, motion, development and reproduction in plants, fungi, bacteria. Bacterial phytochromes commonly function as an entrance signal two-component sensory systems. Despite availability of three-dimensional structures other proteins, conformational changes, which lead activation protein, are not understood. We reveal cryo electron microscopy complete phytochrome from Deinoccocus radiodurans its resting photoactivated...
Abstract Charge-transfer reactions in proteins are important for life, such as photolyases which repair DNA, but the role of structural dynamics remains unclear. Here, using femtosecond X-ray crystallography, we report changes that take place while electrons transfer along a chain four conserved tryptophans Drosophila melanogaster (6-4) photolyase. At femto- and picosecond delays, photoreduction flavin by first tryptophan causes directed responses at key asparagine, salt bridge,...
In the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are significant interest. present study, we dissect three proline in core region rat IAPP into single-point at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy solve structures 6 polymorphs formed by these mutants, revealing peptide's self-assembly patterns identifying critical interactions that...
Membrane proteins are embedded in a lipid bilayer and maintain strong interactions with molecules. Tightly bound lipids responsible for vertical positioning integration of the membrane assembly multisubunit complexes occasionally act as substrates. In this work we present lipidic sponge phase crystal structure reaction center from Blastochloris viridis to 1.86 A, which reveals molecules interacting protein surface. A diacylglycerol molecule is bound, through thioether bond, N-terminus...
Mammalian cell surfaces are decorated with complex glycoconjugates that terminate negatively charged sialic acids. Commensal and pathogenic bacteria can use host-derived acids for a competitive advantage, but require functional acid transporter to import the sugar into cell. This work investigates sodium symporter (SiaT) from Staphylococcus aureus (SaSiaT). We demonstrate SaSiaT rescues an Escherichia coli strain lacking its endogenous when grown on N-acetylneuraminic (Neu5Ac) or...
Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP provide broad framework understand how they work, but the mechanistic details transport not yet defined. Here we report cryo-EM structure Haemophilus influenzae N -acetylneuraminate transporter ( Hi SiaQM) at 2.99 Å...
Antibiotic resistance is a major worldwide concern, and new drugs with mechanistically novel modes of action are urgently needed. Here, we report the structure-based drug design, synthesis, evaluation in vitro cellular systems sialic acid derivatives able to inhibit bacterial symporter SiaT. We designed synthesized 21 screened their affinity for SiaT by thermal shift assay elucidated inhibitory mechanism through binding thermodynamics, computational methods, kinetic studies. The most potent...
Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP provide broad framework understand how they work, but the mechanistic details transport not yet defined. Here we report cryo-EM structure Haemophilus influenzae N-acetylneuraminate transporter (HiSiaQM) at 2.99 Å resolution...
Phytochromes (PHYs) are photoreceptor proteins first discovered in plants, where they control a variety of photomorphogenesis events. PHYs as photochromic can reversibly switch between two distinct states: red light (Pr) and far-red (Pfr) absorbing form. The discovery Bacteriophytochromes (BphPs) nonphotosynthetic bacteria has opened new frontiers our understanding the mechanisms by which these natural photoswitches single cell development, although role BphPs vivo remains largely unknown....
The mechanism of serine proteases prominently illustrates how charged amino acid residues and proton transfer events facilitate enzyme catalysis. Here we present an ultrahigh resolution (0.93 Å) x-ray structure a complex formed between trypsin canonical inhibitor acting through substrate-like mechanism. electron density indicates the protonation state all catalytic where histidine is, as expected, in its neutral prior to acylation step by serine. carboxyl group aspartate displays asymmetric...
The structural response of the drosophila (6-4) photolyase to photoinduced electron transfer along a chain tryptophans is revealed using serial crystallographic snapshot protein in its radical pair state.
LC8 dynein light chains (DYNLL) are conserved homodimeric eukaryotic hub proteins that participate in diverse cellular processes. Among the binding partners of DYNLL2, myosin 5a (myo5a) is a motor protein involved cargo transport. Here we provide profound characterization DYNLL2 motif myo5a free and DYNLL2-bound form by using nuclear magnetic resonance spectroscopy, X-ray crystallography, molecular dynamics simulations. In form, region, located an intrinsically disordered domain tail, has...
Summary The process of obtaining a well‐expressing, soluble and correctly folded constructs can be made easier quicker by automating the optimization cloning, expression purification. While there are many semiautomated pipelines available for purification, is hardly any pipeline that involves complete automation. Here, we achieve automation all steps involved in cloning vivo screening. This demonstrated using 18 genes sialic acid catabolism surface sialylation pathway. Our main objective was...