Research Lab

(Bio)molecular Structure and Interactions by NMR

(Bio)molecular Structure and Interactions by NMR
29670
Research Interests

Our main research interests are related to the application and development of solution state nuclear magnetic resonance (NMR) spectroscopy for structural analysis and the study of intermolecular interactions in biological and chemical systems. In the context of the functional analysis of catalytic systems and the understanding of molecular recognition processes we explore: (i) protein-ligand interactions in drug discovery; (ii) solute-solvent interactions; (iii) protein structure and dynamics (iv) new techniques in NMR.

Research Highlights
Studying intermolecular interactions in complex media

Cells are inherently crowded, under molecular crowding (MC) conditions specific molecular recognition events and interactions may occur, that could remain undetectable under diluted solutions. We have recently used NMR to study the formation of large molecular size protein complexes driven by protein-glycan interactions under MC conditions demonstrating that glycosylation can be a player in quinary structure and in the organization of the cellular environment at the molecular level (CHEM. EUR. J., 2017; 23, 13213). Another of our main research interests is the study of molecular recognition processes in alternative complex media. By combining different NMR experiments we have been studying ion-pair interactions in ionic liquids in order to understand their supramolecular structure and better explore their biochemical applications (MAGN. RESON. CHEM., 2018, 56, 127).

fig1Protein-Glycan Quinary Interactions in Crowding Environment Unveiled by NMR Spectroscopy

 

Structural insights into mucin glycosylation and recognition

Glycans play a key role in distinct molecular mechanisms in health and disease. In this context, the projects (IF/00780/2015 and PTDC/BIA-MIB/31028/2017) investigate the mucin-derived cancer-related glycophenotype. By employing NMR in tandem with molecular modeling and biophysical techniques, the projects exploit the structural features of mucin glycosylation (NAT. COMMUN. 2017; 5, 1959; CHEM. EUR. J. 2018; 24, 8382) and the molecular recognition of mucin-derived tumour-associated carbohydrate antigens (TACAs) (J. AM. CHEM. SOC. 2015, 137, 12438) for a structure-guided rational design of glycan-based cancer therapies.

fig2Structural Insights on Glycans for Cancer Therapies

 

Representative Projects

  • Evaluation of ionic liquids for CO2 capture in exhaust gases”, PETROBRAS SA., Total and Unit funding: €110,000, Eurico Cabrita (PI).
  • “Advances into the Glycome: From a structural viewpoint to function in human health and disease”, IF/00780/2015, FCT-MCTES, Total and Unit funding: €50,000, Filipa Marcelo (PI).
  • “Advances in MUC1 Glycan Cancer Antigens: From structure to function in the fight against cancer”, FCT-MCTES, Total funding: €238,195, Unit funding: €176,266, Filipa Marcelo (PI).

Selected Publications

de las Rivas, Matilde; Paul Daniel, Earnest James; Narimatsu, Yoshiki; Compañón, Ismael; Kato, Kentaro; Hermosilla, Pablo; Thureau, Aurélien; et al. 2020. Molecular basis for fibroblast growth factor 23 O-glycosylation by GalNAc-T3. Nature Chemical Biology, 16(3), DOI: 10.1038/s41589-019-0444-x
Viegas, Aldino; Dollinger, Peter; Verma, Neha; Kubiak, Jakub; Viennet, Thibault; Seidel, Claus AM; Gohlke, Holger; et al. 2020. Structural and dynamic insights revealing how lipase binding domain MD1 of Pseudomonas aeruginosa foldase affects lipase activation. Scientific Reports, 10(1), DOI: 10.1038/s41598-020-60093-4
Gomes, AS; Ramos, H; Gomes, S; Loureiro, JB; Soares, J; Barcherini, V; Monti, P; Fronza, G; Oliveira, C; Domingues, L; Bastos, M; Dourado, DFAR; Carvalho, AL; Romão, MJ; Pinheiro, B; Marcelo, F; Carvalho, A; Santos, MMM; Saraiva, L. 2020. SLMP53-1 interacts with wild-type and mutant p53 DNA-binding domain and reactivates multiple hotspot mutations. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 1864(1), DOI: 10.1016/j.bbagen.2019.129440
Aldino Viegas, Dongsheng M. Yin, Jan Borggräfe, Thibault Viennet, Marcel Falke, Anton Schmitz, Michael Famulok, Manuel Etzkorn. 2019. Molecular Architecture of a Network of Potential Intracellular EGFR Modulators: ARNO, CaM, Phospholipids, and the Juxtamembrane Segment. STRUCTURE, DOI: 10.1016/j.str.2019.11.001
Diana ORibeiro; Aldino Viegas; Virgínia MRPires; João Medeiros‐Silva; Pedro Bule; Wengang Chai; Filipa Marcelo; Carlos MGAFontes; Eurico JCabrita; Angelina SPalma; Ana Luísa Carvalho. 2019. Molecular basis for the preferential recognition of β1,3‐1,4‐glucans by the family 11 carbohydrate‐binding module from Clostridium thermocellum. The FEBS Journal, DOI: 10.1111/febs.15162