Biological NMR

Structural Elucidation and Remodeling of Fungal Cell Wall by Solid-state NMR

Isha Gautam -

Understanding cell wall architecture and adaptation mechanism is essential for antifungal drug efficacies. The cell wall of Aspergillus fumigatus is characterized using solid-state NMR (ssNMR) divulged rigid core of chitin, β-1,3-glucan and α-1,3-glucan. Mobile domains contain galactoproteins and α-1,3-glucan. Hydrophobic and stiff cell walls were exploited in response to antifungals.

Probing the dynamics of YadA autotransporter in microcrystals and outer membranes hints at requirements for beta-barrel membrane insertion

Jayasubba Reddy Yarava - @JYarava

Most types of cells are protected and functionalized by a dense surface layer of glycans, proteoglycans, and glycolipids. This surface represents an under-explored space in structural biology that is almost impossible to recreate in vitro. Here, a realistic picture of YadA dynamics in asymmetric outer membrane environment was investigated using ssNMR and MD simulations.

Yesterday's Software for Tomorrow's Solutions!

Simon P. Skinner - @nmronline

Host-guest interactions in MOFs are key to their performance in various applications. Solid-state NMR can probe these interactions, however, with limited sensitivity. I will demonstrate how endogenous metal-ion DNP can tackle this challenge, keeping MOF pores empty for guests, and discuss the effect of MOFs mobility and molecular O2 on the DNP efficacy.

NMR metabolomics to detect cancer cell

Sofia Mariasina and Kamil Aysin - @SMariasina and @Aysin_Kamil

We study new chromosomal rearrangements possibly causing lung cancer. We take human cell lines and reproduce in vitro mutations found in the tumors of cancer patients and test them for malignant transformation. Since cancer cells metabolism differs significantly from normal one we can use NMR metabolomics to detect malignancy

The molecular mechanism of vancomycin by ssNMR

Shadan Geshani - @ShGeshani

Vancomycin is a clinically-used glycopeptide antibiotic, used for the treatment of severe infections. Vancomycin kills bacteria by targeting cell wall precursors in the bacterial membrane, however, resistance mechanisms against this antibiotic have been widely known in pathogenic species. Molecular details of vancomycin’s action could only be studied in the absence of membranes. A better understanding of the molecular mechanism of vancomycin by ssNMR at atomic level will help to overcome this problem.

"Dark" phosphate no longer dark?

Jiaqi Lu - @Jiaqi_Lu22

Our research has unveiled the existence of hidden phosphate clusters, eluding spectroscopic detection. By manipulating solution conditions, notably pH, we expose their intricate behavior. Employing the power of chemical exchange saturation transfer, we discover new spectroscopic features, and provide further evidence for clustering. These results are important for studying phosphate function in the physiological environment.

The power of 19F-NMR: peptide-membrane binding is not that basic!

Tran Thanh Tam Pham - @tammyphamily

My research focuses on a hormone, Apelin, important in forming new blood vessels and progressing chronic illnesses. It is not uncommon for peptides like Apelin to bind membrane before receptor-binding. Using 19F-Nuclear Magnetic Resonance, I characterize this binding suggesting a mechanism for Apelin that highlights membrane role in therapeutic delivery.

Hunting evidence of aggregation in ADP and the influence of ion binding

Kelsey Marr - @kelsey_marr

Magnesium is the most abundant divalent cation in the cell and essential to nearly every biochemical reaction involving adenosine triphosphate and its lower energy counterpart, adenosine diphosphate. This work has focused on using 31P and 1H NMR as a tool to understand chemical and molecular interactions between ADP and Mg for evidence of nucleotide aggregation either by self-association or influenced by cations.

Study of phosphorus clusters in tau fragment fibrils via multiple quantum solid-state NMR under DNP

Lokeswara Rao - @lokeswarnmr

Hyperphosphorylation of the protein tau is a characteristic of neurodegenerative diseases, yet its role is not entirely clear in promoting the tau aggregation propensity. Multiple quantum spin counting experiments were carried out to probe the phosphate species clustering and beta-sheet organization in the fibrils of phosphorylated tau fragments.

Solid-state NMR revealed peculiar phosphonate in velvet worm slime

Alexandre Poulhazan - @AlexPoulhazan

Velvet worms are fascinating animals that have a peculiar way to hunt. They eject a translucent liquid, the slime, that quickly forms sticky fibers trapping their preys. In addition to exciting recyclability of this natural glue, this slime has been characterized here by MAS-DNP and NMR, detecting unprecedented phosphonate-rich molecules.

Altering a protein’s conformational space differentially regulates the host signalling pathway

Apurva phale - @ApurvaPhale

Viruses mimic host proteins to evade their immune response. A few baculoviruses do this by mimicking a widely present protein, ubiquitin. Interestingly, this viral protein can differentially regulate the forward and reverse pathways, not by changing the interaction interface but by modulating the protein's conformational space as observed by eCPMG-NMR.

Conformational Plasticity of Parallel G-quadruplex – Implications on Duplex-Quadruplex Motifs

Rajesh Kumar Reddy Sannapureddi - @RR_Sannapureddi

Parallel G-quadruplexes formed by guanine rich sequences are ubiquitously formed in promoter, telomere regions. Structural and dynamic features associated with them is presented in details from structure survey, solution state NMR studies and MD simulations. Impact of covalently attached duplex on parallel quadruplex discerned from NMR studies are presented.

NMR spectroscopy in the light of supercritical fluid technologies

Konstantin Belov - @SCFsci

Determination of the predominant conformation of small molecules of drug in solution is one of the fundamental tasks of modern pharmaceutical and physical chemistry. Our research group "Fluid State NMR" has proposed a number of technical and methodological ways to solve this problem in the supercritical fluid environment.

Partitioning of small molecules in biomolecular condensates

Julie Maibøll Buhl - @ll_buhl95024

The environment of biomolecular condensates, formed by LLPS, can be investigated using determined partitioning coefficients from a wide range of molecules. The time-zero 1H-13C HSQC was proposed and tested on a model system, where repetitions of the pulse sequence allows for correction of signal attenuation leading to precise quantification.

Exploring the Effect of Aerogel on Mefenamic Acid Structure and Properties

Valentina Sobornova - @VSobornova7121

The effect of mefenamic acid on the physicochemical and sorption properties of aerogel was studied. 1H and 13C MAS, T1-T2 RRCOSY and 1H-1H NOESY NMR experiments were carried out to study the conformational state of mefenamic acid and its effect on the aerogel structure. The results show that the group fraction of conformer groups of mefenamic acid changes by 53% in the presence of aerogel.

Nuclear Magnetic Resonance spectroscopy technique for Identification of Designer Drugs

Annwesha Mazumdar - @Annwesha9

It’s a challenging task to detect the metabolites of designer drugs in the body. NMR spectroscopy is one of the validating techniques for its utility of metabolic fingerprinting of various designer drugs and has opened a new horizon in forensics. This paper highlights the recent developments of Nuclear Magnetic Resonance spectroscopy applied for the Forensic identification of various designer drugs.

Chemical Shift Imaging NMR for Probing Bacterial-Mammalian Crosstalk in the Human Large Intestine

Trey Koev - @TTKoev

Chemical shift imaging NMR allows us to exploit a naturally occurring gradient of commensal bacteria, mucosa and large intestinal colonocytes. Probing the metabolic crosstalk between bacteria and colonocytes in healthy and diseases (cancer) cell set-ups allows us to probe differences in the cell-cell communication on a molecular level, potentially enabling the development of novel treatment avenues for colorectal pathologies.

Imaging and spectroscopic applications in cancer research

Madhu Basetti - @mbasetti

We are an imaging core group working in cancer research with preclinical imaging modalities for early detection and prognosis of cancer.

NMR experiments to study inhibition of enzymes that confer bacterial resistance

Yara Lins Rocha - @YaraLRocha

Enzymes belonging to the Carbapenem-Hydrolyzing Class D β-lactamases (CHDL's) confer bacterial resistance to β-lactam antibiotics and are often associated with outbreaks involving the pathogenic bacteria Acinetobacter baumannii. We report the inhibition of CHDL OXA-143 by the reaction product with meropenem, a carbapenem antibiotic, in addition to describing its effect on protein structure and dynamics. Kinetic 1H-NMR experiments were performed to assess how hMER interferes with the catalytic efficiency of the enzyme against ampicillin and meropenem itself, indicating a clear inhibition. Chemical shift perturbation (CSP) was performed using 15N-HSQC and 15N-TROSY titration experiments. The results indicate that hMER acts as a competitive inhibitor blocking the active site and decreasing the dynamics of essential motifs around the binding site.