Protein stability (thermodynamic and kinetic) drives the biophysical properties of the polypeptide chain (protein folding) and the protein's concentration in the cellular environment (protein homeostasis). It is the result of a delicate balance between inter- and intramolecular interactions, which can be easily altered by mutations and/or upon changes in the composition of the surrounding media. In this context, NMR spectroscopy offers a plethora of suitable experiments to investigate protein stability. In our laboratory we are currently interested in the following topics:
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Pharmacological chaperones. Rare diseases (~7000 identified to date) are an area of significant medical need affecting an estimated 350 million people worldwide, with ~95% having no currently approved drug treatment. They are often produced by inherited mutations affecting the activity of a protein and It is becoming increasily clear that, most frequently, a mutation destabilizes the protein/enzyme, ultimately affecting its intracellular homeostasis. In this context, pharmacological chaperones (small molecules which bind to the protein, restoring stability and activity without affecting its function) can be applied to many diseases. In our laboratory we are investigating new methods (NMR, biophysical and biochemical) for the discovery and characterization of pharmacological chaperones against a set of diseases: congenital eryhtropoietic porphyria, tyrosianemia.
- Environmental modulation of enzyme stability. The high catalytic efficiency and the exquisite enantioselectivity of an enzyme has been employed in some industrial processes to upgrade their properties in order to make them more environmentally-friendly. However, large scale industrial implementation of biotechnological reactions is often limited by the marginal stability of the enzyme in the reactor conditions. In our laboratory we employ NMR and circular dichroism to investigate the effect of external crowding agents to improve the activity and stability of several enzymes. Specifically, we are investigating the mechanism for protein haloadaptation by a combined use of site directed mutagenesis and high-resolution NMR spectroscopy.
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General Director
José M Mato
IMI2 Programme -
Principal Investigator
Óscar Millet
IKERBASQUE RESEARCH FELLOW -
Gabriel Ortega Quintanilla
Ikerbasque Research Fellow RESEARCH ASSISTANT -
Fernando Lopitz Otsoa
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Nieves Embade
SPECIALIST -
Rubén Gil Redondo
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Beatriz González Valle
POST DOCTORAL RESEARCHER -
Andreas Schedlbauer
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David Fernández Ramos
TECHNICIANS / DOCTORAL CANDIDATES -
Virginia Gutiérrez de Juan
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Jon Bilbao García
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Pablo Herrero Alfonso
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Maria de los Reyes Luque Urbano
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Ángela de Diego Rodríguez
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Nerea Adriana Igartua Mendia
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Chiara Bruzzone
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Ricardo Diogo Alves Conde
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Tania Pereira Ortuzar
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Ana Laín
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Jon Gil Martinez
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Riccardo Scarin
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Maider Bizkarguenaga Uribiarte
Members
Latest Publications
Inhibition of carnitine palmitoyltransferase 1A in hepatic stellate cells protects against fibrosis
Fondevila, MF;Fernandez, U;Heras, V;Parracho, T;Gonzalez-Rellan, MJ;Novoa, E;Porteiro, B;Alonso, C;Mayo, R;Lima, ND;Iglesias, C;Filliol, AA;Senra, A;Delgado, TC;Woodhoo, A;Herrero, L;Serra, ...
JOURNAL OF HEPATOLOGY
2022-07-01
Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
Martinez-Arranz, I;Bruzzone, C;Noureddin, M;Gil-Redondo, R;Minchole, I;Bizkarguenaga, M;Arretxe, E;Iruarrizaga-Lejarreta, M;Fernandez-Ramos, D;Lopitz-Otsoa, F;Mayo, R;Embade, N;Newberry, E;Mittendorf, ...
HEPATOLOGY
2022-03-17
Exploration of Human Serum Lipoprotein Supramolecular Phospholipids Using Statistical Heterospectroscopy in n-Dimensions (SHY-n): Identification of Potential Cardiovascular Risk Biomarkers Related to SARS-CoV-2 Infection
Masuda, R;Lodge, S;Whiley, L;Gray, N;Lawler, N;Nitschke, P;Bong, SH;Kimhofer, T;Loo, RL;Boughton, B;Zeng, AX;Hall, D;Schaefer, H;Spraul, M;Dwivedi, G;Yeap, BB;Diercks, T;Bernardo-Seisdedos, ...
ANALYTICAL CHEMISTRY
2022-03-15
PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer
Zabala-Letona, A;Arruabarrena-Aristorena, A;Fernandez-Ruiz, S;Viera, C;Carlevaris, O;Ercilla, A;Mendizabal, I;Martin, T;Macchia, A;Camacho, L;Pujana-Vaquerizo, M;Sanchez-Mosquera, P;Torrano, ...
ONCOGENESIS
2022-02-23
Depletion of mitochondrial methionine adenosyltransferase alpha 1 triggers mitochondrial dysfunction in alcohol-associated liver disease
Barbier-Torres, L;Murray, B;Yang, JW;Wang, JH;Matsuda, M;Robinson, A;Binek, A;Fan, W;Fernandez-Ramos, D;Lopitz-Otsoa, F;Luque-Urbano, M;Millet, O;Mavila, N;Peng, H;Ramani, K;Gottlieb, R;Sun, ...
NATURE COMMUNICATIONS
2022-01-28
J-Edited DIffusional Proton Nuclear Magnetic Resonance Spectroscopic Measurement of Glycoprotein and Supramolecular Phospholipid Biomarkers of Inflammation in Human Serum
Nitschke, P;Lodge, S;Kimhofer, T;Masuda, R;Bong, SH;Hall, D;Schafer, H;Spraul, M;Pompe, N;Diercks, T;Bernardo-Seisdedos, G;Mato, JM;Millet, O;Susic, D;Henry, A;El-Omar, EM;Holmes, E;Lindon, ...
ANALYTICAL CHEMISTRY
2022-01-05
S-adenosylmethionine inhibits la ribonucleoprotein domain family member 1 in murine liver and human liver cancer cells
Ramani, K;Robinson, AE;Berlind, J;Fan, W;Abeynayake, A;Binek, A;Barbier-Torres, L;Noureddin, M;Nissen, NN;Yildirim, Z;Erbay, E;Mato, JM;Van Eyk, JE;Lu, SC
HEPATOLOGY
2021-12-18
Uneven metabolic and lipidomic profiles in recovered COVID-19 patients as investigated by plasma NMR metabolomics
Bizkarguenaga, M;Bruzzone, C;Gil-Redondo, R;SanJuan, I;Martin-Ruiz, I;Barriales, D;Palacios, A;Pasco, ST;Gonzalez-Valle, B;Lain, A;Herrera, L;Azkarate, A;Vesga, MA;Eguizabal, C;Anguita, J;Embade, ...
NMR IN BIOMEDICINE
2021-10-27
Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests
Masoodi, M;Gastaldelli, A;Hyotylainen, T;Arretxe, E;Alonso, C;Gaggini, M;Brosnan, J;Anstee, QM;Millet, O;Ortiz, P;Mato, JM;Dufour, JF;Oresic, M
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
2021-09-10
O-GlcNAcylated p53 in the liver modulates hepatic glucose production
Gonzalez-Rellan, MJ;Fondevila, MF;Fernandez, U;Rodriguez, A;Varela-Rey, M;Veyrat-Durebex, C;Seoane, S;Bernardo, G;Lopitz-Otsoa, F;Fernandez-Ramos, D;Bilbao, J;Iglesias, C;Novoa, E;Ameneiro, ...
NATURE COMMUNICATIONS
2021-08-20