Welcome
Interests.
Since my undergraduate day I have been interested in the ATP synthase, the protein complex responsible for the synthesis of ATP coupled to the respiratory chain.
The ATP synthase is a very complex enzyme, it is formed by at least 15 different subunits spanning soluble and membrane embeded domains. Its kinetics follow a positive cooperativity for catalysis while it follows a negative cooperativity for substrate binding. As I mentioned earlier, the enzime has as its substrates ADP and Pi, and of course, a electrochemical gradient.
My research interest are related to various aspects and levels of the ATP synthase. At the mitochondrial level, the way the structure and the function of the ATP synthase affects the ultrastructure of the mitochondria, that is, its cristae. At the whole molecule level, the way in which its different subunits interact to bring about the function of the complex, either during ATP hydrolysis or ATP synthesis. At the single polypeptide level, looking at how certain tertiary structure "encode" mechanical properties of each of the subunits of the ATP synthase.
Currently, I am working with the TIM. TIM is a very interesting enzyme in its own right. Its function is the isomerization of glyceraldehyde-3-phospate to dihydroacetone-phosphate. Since its catalyses this reaction so fast, it has been called a "perfect" enzyme. This allows for experiments in conditions not easily accesible for other enzymes. Added to its archetypical TIM-Barrel dimeric structure, TIM is an excellent model to probe protein folding, design, and kinetics.
My favorite proteins.
This is a small image representing my three current protein interests (from right to left): the Triosephosphate Isomerase (TIM, in this case from yeast), the endogenous bovine inhibitory protein (IF1) and the ATP synthase. Each is a complex system in its own right.
Current Research.
Right now I am working in the molecular dynamics of the IF1, dissecting is motions and their relevance to the known mechanism of function. This has been done mainly by selecting a reduced model of the IF1 and by changing the protonation state of key residues. This idea was born at the Dr. Marietta Tuena's lab, at the Instituto de Fisiología Celular, UNAM.
Other project is the determination of the atomic structure of a complex between the F1 ATPase and the IF1. Crystals suitable for diffraction have been obtained and we are now working in the resolution of the structure via molecular replacement. This work is colaboration with Dr. Adela Rodríguez at the Insituto de Química, UNAM.
A colaboration with Dr. Alejandro Sosa Peinado (Facultad de Medicina, UNAM) involves the extensive use of docking, molecular dynamics and protein design to engineer novel affinities into a aminoacid binding protein from bacteria.
At last, but not least, we are also using docking and protein design to create TIMs that can bind different molecules at places distant from the catalytic site. This project is directed by Dr. Alejandro Fernandez Velazco at the Facultad de Medicina, UNAM.
