X-Ray Crystallography of Membrane Proteins

X-Ray Crystallography of Membrane Proteins

This research program has two main and complementary focuses: structure-function of integral membrane proteins and structure-based drug discovery & design.

The projects developed in this program are focused on determining the crystal structure of membrane proteins and, the development of biomedical or biotechnological applications based on the solved high resolution structure. For instance, the atomic structure of the proton-gated urea channel from Helicobacter pylori provides a template for the development of inhibitors that might lead to simple targeted monotherapy to prevent peptic ulcer disease, and reduce the incidence of gastric adenocarcinoma. An additional goal is solving the atomic structure of membrane proteins in cubic lipid phases at very high resolution (1.55 Å) and in different conformation. A case in point is the light-driven ion pump bacteriorhodopsin crystallized in the ground state using crystallization and several photocycle intermediates “frozen in mid-stroke”. This has allowed developing a detailed atomic mechanism of ion pumping which will permit to develop optogenetic biotechnological applications based on genetically engineered mutants. Other structure-function studies are related with cancer-associated proteins (like Annexin, S100 proteins and p53), and aimed to develop structured-based antitumoral compounds. Moreover, other proteins of interest are the trypanosomal TUTase that is used for virtual ligand screening of compounds with anti-trypanosomal activity


Senior Researchers