A5045032471- Enzyme Structure and Function
- Drug Transport and Resistance Mechanisms
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- Metal-Catalyzed Oxygenation Mechanisms
- Trace Elements in Health
- Microbial bioremediation and biosurfactants
- Bacteriophages and microbial interactions
- Folate and B Vitamins Research
- Microbial metabolism and enzyme function
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- HER2/EGFR in Cancer Research
- Antibiotic Resistance in Bacteria
- Fungal and yeast genetics research
- Redox biology and oxidative stress
- Protein Structure and Dynamics
- Aldose Reductase and Taurine
Antibiotic (Bulgaria)
2023-2025
University of Gothenburg
2016-2025
Sahlgrenska University Hospital
2020-2022
Stanford University
2016-2017
Stanford Medicine
2017
Uppsala University
2009-2011
Diamond Light Source
2011
University of Oslo
2009-2011
Oslo University Hospital
2009
Swedish University of Agricultural Sciences
2002-2008
Aquaporins are membrane channels that facilitate the flow of water across biological membranes. Two conserved regions central for selective function: dual asparagine-proline-alanine (NPA) aquaporin signature motif and aromatic arginine selectivity filter (SF). Here, we present crystal structure a yeast at 0.88 angstrom resolution. We visualize H-bond donor interactions NPA motif's asparagine residues to passing molecules; observe polarized water-water configuration within channel; assign...
N -Acetylneuraminic acid (Neu5Ac) is a negatively charged nine-carbon amino sugar that often the peripheral in human cell-surface glycoconjugates. Some bacteria scavenge, import, and metabolize Neu5Ac or redeploy it on their cell surfaces for immune evasion. The import of by many mediated tripartite ATP-independent periplasmic (TRAP) transporters. We have previously reported structures SiaQM, membrane-embedded component Haemophilus influenzae TRAP transport system, (Currie et al., 2024)....
Overexpression of the epidermal growth factor (EGF) receptor (EGFR) in cancer cells correlates with tumor malignancy and poor prognosis for patients. For this reason, EGFR has become one main targets anticancer therapies. Structural data obtained last few years have revealed molecular mechanism ligand-induced dimerization subsequent signal transduction, also how is blocked by either monoclonal antibodies or small molecules. Nimotuzumab (also known as h-R3) a humanized antibody that been...
Transcription is regulated through binding factors to gene promoters activate or repress expression, however, the mechanisms by which find targets remain unclear. Using single-molecule fluorescence microscopy, we determined in vivo stoichiometry and spatiotemporal dynamics of a GFP tagged repressor, Mig1, from paradigm signaling pathway Saccharomyces cerevisiae. We repressor operates clusters, upon extracellular signal detection, translocate cytoplasm, bind nuclear turnover. Simulations Mig1...
Abstract In bacteria and archaea, tripartite ATP-independent periplasmic (TRAP) transporters uptake essential nutrients. TRAP receive their substrates via a secreted soluble substrate-binding protein. How sodium ion-driven secondary active transporter is strictly coupled to protein poorly understood. Here we report the cryo-EM structure of sialic acid SiaQM from Photobacterium profundum at 2.97 Å resolution. SiaM comprises “transport” domain “scaffold” domain, with transport consisting...
Pectin is a principal component in the primary cell wall of plants. During development, pectin modified by methylesterases to give different properties wall. This report describes first crystal structure plant methylesterase. The β‐helical embodies central cleft, lined several aromatic residues, that has been deduced be suitable for binding. active site found at center this cleft where Asp157 suggested act as nucleophile, Asp136 an acid/base and Gln113/Gln135 form anion hole stabilize...
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
Human dihydroorotate dehydrogenase ( hDHODH) catalyzes the rate-limiting step in de novo pyrimidine biosynthesis, conversion of to orotate. hDHODH has recently been found be associated with acute myelogenous leukemia, a disease for which standard intensive care not changed over decades. This work presents novel class inhibitors, are based on an unusual carboxylic group bioisostere 2-hydroxypyrazolo[1,5- a]pyridine, that designed starting from brequinar, one most potent inhibitors. A...
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...
N -Acetylneuraminic acid (Neu5Ac) is a negatively charged nine-carbon amino-sugar that often the peripheral sugar in human cell-surface glycoconjugates. Some bacteria scavenge, import, and metabolize Neu5Ac or redeploy it on their cell surfaces for immune evasion. The import of by many mediated tripartite ATP-independent periplasmic (TRAP) transporters. We have previously reported structures SiaQM, membrane-embedded component Haemophilus influenzae TRAP transport system, (Currie et al.,...
Bacterial Rieske non-heme iron oxygenases catalyze the initial hydroxylation of aromatic hydrocarbon substrates. The structures all three components one such system, toluene 2,3-dioxygenase have now been determined. This system consists a reductase, ferredoxin and terminal dioxygenase. dioxygenase, which was cocrystallized with toluene, is heterohexamer containing catalytic structural subunit. subunit contains [2Fe–2S] cluster mononuclear at active site. not strongly bound easily removed...
Sodium-dependent glucose transporters (SGLTs) exploit sodium gradients to transport sugars across the plasma membrane. Due their role in renal sugar reabsorption, SGLTs are targets for treatment of type 2 diabetes. Current therapeutics phlorizin derivatives that contain a moiety bound an aromatic aglycon tail. Here, we develop structural models human SGLT1/2 complex with inhibitors by combining computational and functional studies. Inhibitors bind pocket tail extracellular vestibule. The...
Abstract Bacteria respond to environmental changes by inducing transcription of some genes and repressing others. Sialic acids, which coat human cell surfaces, are a nutrient source for pathogenic commensal bacteria. The Escherichia coli GntR-type transcriptional repressor, NanR, regulates sialic acid metabolism, but the mechanism is unclear. Here, we demonstrate that three NanR dimers bind (GGTATA) 3 -repeat operator cooperatively with high affinity. Single-particle cryo-electron microscopy...
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...