Research Lab

XTAL - Macromolecular Crystallography

XTAL - Macromolecular Crystallography
Research Interests

We use structural molecular biology tools to study proteins and protein-ligand complexes, using X-ray Crystallography, Small Angle X-ray Scattering (SAXS) and other biohysical methods.


Our main research areas are:

  1. Mechanistic studies (metalloenzymes, in particular those containing Mo, W and Fe centers, with impact on health and on the environment);
  2. Drug metabolism and ligand discovery;
  3. Glycan-protein and protein-protein interactions;
  4. Novel strategies for improved protein crystallization.
Research Highlights
Discovering 3D structures of proteins to clarify enzymatic mechanisms and understand function


a) Reduction of CO2 to formate – only few  enzymes in nature can chemically convert carbon dioxide, the greenhouse gas, into useful products. We could unveil new molecular features and add new insights to the catalytic mechanism of a tungstendependent formate dehydrogenase. This knowledge will prompt to design and analyse mechanistic relevant variants towards a more efficient enzyme.

b) Drug Metabolism – Human aldehyde oxidase (hAOX1) is an enzyme of emerging importance in phase I drug metabolism that we have extensively studied (complexes and variants). Recently we have computationaly studied its catalytic mechanism that enabled a deeper understanding of the intricacies of hAOX1 reactivity. This will help to tune drug candidates with impact in drug discovery.


highlight 2020

Representative Projects

  • “Glycan-human microbiome interaction: glycan diversity and recognition in the human gut with impact on health and nutrition”, FCT-MCTES, Total funding: €234,280, Unit funding: € 176,405 + € 15,625 (NZYTech) , Maria Angelina de Sá Palma (PI).
  • “Advances in MUC1 Glycan Cancer Antigens: From structure to function in the fight against cancer”, FCTMCTES, Total funding: €238,195, Unit funding: € 176,266 , Maria Angelina de Sá Palma (Co-PI).
  • “B.EST.CBM: an integrative structural biology approach to characterise the protein-carbohydrate microbial recognition”, FCT-MCTES, Total funding: €199,884, Unit funding: €120,684, Ana Luísa Carvalho (PI).
  • “Carbon monoxide guided shuttles (COGSs) to fight rheumatoid arthritis”, FCT-MCTES, Total funding: €199,996, Unit funding: €117,996, Teresa Santos-Silva (PI).
  • “Aldehyde oxidases in drug metabolism and biocatalysis: searching for the substrate specificity and catalytic mechanism”, FCT-MCTES, Total funding: €198,996, Unit funding: €162,792, Maria João Romão (PI).

Selected Publications

dos Santos, R; Iria, I; Manuel, AM; Leandro, AP; Madeira, CAC; Goncalves, J; Carvalho, AL; Roque, ACA. 2020. Magnetic Precipitation: A New Platform for Protein Purification. Biotechnology Journal, 15, DOI: 10.1002/biot.202000151
Oliveira, AR; Mota, C; Mourato, C; Domingos, RM; Santos, MFA; Gesto, D; Guigliarelli, B; Santos-Silva, T; Romao, MJ; Pereira, IAC. 2020. Toward the Mechanistic Understanding of Enzymatic CO2 Reduction. ACS Catalysis, 10, DOI: 10.1021/acscatal.0c00086
Campanero-Rhodes, MA; Palma, AS; Menendez, M; Solis, D. 2020. Microarray Strategies for Exploring Bacterial Surface Glycans and Their Interactions With Glycan-Binding Proteins. Frontiers in Microbiology, 10, DOI: 10.3389/fmicb.2019.02909
Alves-Barroco, C; Paquete-Ferreira, J; Santos-Silva, T; Fernandes, AR. 2020. Singularities of Pyogenic Streptococcal Biofilms - From Formation to Health Implication. Frontiers in Microbiology, 11, DOI: 10.3389/fmicb.2020.584947
Terao, M; Garattini, E; Romao, MJ; Leimkuhler, S. 2020. Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes. JOURNAL OF BIOLOGICAL CHEMISTRY, 295, DOI: 10.1074/jbc.REV119.007741