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 -
Gabriel Ortega Quintanilla
Ikerbasque Research Fellow - Ramón y Cajal (RyC) Programme RESEARCH ASSISTANT -
Fernando Lopitz Otsoa
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Nieves Embade
SPECIALIST -
Beatriz González Valle
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Rubén Gil Redondo
POSTDOCTORAL RESEARCHER -
Ganeko Bernardo
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Andreas Schedlbauer
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David Fernández Ramos
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Alain Ibañez de Opakua Lopez de Abetxuko
TECHNICIANS / DOCTORAL CANDIDATES -
Cristina Garrido
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Maria de los Reyes Luque Urbano
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Maider Bizkarguenaga Uribiarte
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Karen Salua Alarcón Morales
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Margarita Gómez Galán
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Alba Pejenaute Pejenaute
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Sara Martín Ramos
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Riccardo Scarin
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Ricardo Diogo Alves Conde
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Laura Gálvez Larrosa
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Virginia Gutiérrez de Juan
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Pablo Herrero Alfonso
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Uxue Hermoso Martínez
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Ana Laín
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Ángela de Diego Rodríguez
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Tania Pereira Ortuzar
Members
Óscar Millet
Latest Publications
Impaired Hepatic Very Low-Density Lipoprotein Secretion Promotes Tumorigenesis and Is Accelerated with Fabp1 Deletion.
Newberry, Elizabeth P; Molitor, Elizabeth A; Liu, Allen; Chong, Kamyar; Liu, Xiuli; Alonso, Cristina; Mato, Jose M; Davidson, Nicholas O;
The American journal of pathology
2024-02-28
Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)
Noureddin, M; Truong, E; Mayo, R; Martínez-Arranz, I; Banales, JM; Mincholé, I; Arrese, M; Cusi, K; Arias-Loste, MT; Bruha, R; Romero-Gómez, M; Iruzubieta, P; Aller, R; Ampuero, J; Calleja, ...
HEPATOLOGY
2024-01-01
S-Adenosylmethionine Negatively Regulates the Mitochondrial Respiratory Chain Repressor MCJ in the Liver
Barbier-Torres, L; Chhimwal, J; Kim, SY; Ramani, K; Robinson, A; Yang, HP; Van Eyk, J; Liangpunsakul, S; Seki, E; Mato, JM; Lu, SC;
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
2024-01-01
Hepatic prohibitin 1 and methionine adenosyltransferase a1 defend against primary and secondary liver cancer metastasis
Fan, W; Cao, DY; Yang, B; Wang, JH; Li, XM; Kitka, D; Li, TWH; You, SY; Shiao, S; Gangi, A; Posadas, E; Di Vizio, D; Tomasi, ML; Seki, E; Mato, JM; Yang, HP; Lu, SC;
JOURNAL OF HEPATOLOGY
2023-12-10
Hepatocyte-specific O-GlcNAc transferase downregulation ameliorates nonalcoholic steatohepatitis by improving mitochondrial function
Gonzalez-Rellan, MJ; Parracho, T; Heras, V; Rodriguez, A; Fondevila, MF; Novoa, E; Lima, N; Varela-Rey, M; Senra, A; Chantada-Vazquez, MDP; Ameneiro, C; Bernardo, G; Fernandez-Ramos, D; Lopitz-Otsoa, ...
MOLECULAR METABOLISM
2023-09-01
Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis
Mózes, FE; Lee, JA; Vali, Y; Alzoubi, O; Staufer, K; Trauner, M; Paternostro, R; Stauber, RE; Holleboom, AG; van Dijk, AM; Mak, AL; Boursier, J; Loup, MD; Shima, T; Bugianesi, E; Gaia, S; Armandi, ...
Lancet Gastroenterology & Hepatology
2023-08-01
Hyperphosphorylation of hepatic proteome characterizes nonalcoholic fatty liver disease in S-adenosylmethionine deficiency
Robinson, AE; Binek, A; Ramani, K; Sundararaman, N; Barbier-Torres, L; Murray, B; Venkatraman, V; Kreimer, S; Mc Ardle, A; Noureddin, M; Fernández-Ramos, D; Lopitz-Otsoa, F; de Juan, VG; Millet, ...
ISCIENCE
2023-02-17
Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19
Bruzzone, C; Conde, R; Embade, N; Mato, JM; Millet, O;
FRONTIERS IN MOLECULAR BIOSCIENCES
2023-02-15
Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes
Cano, A; Vazquez-Chantada, M; Conde-Vancells, J; Gonzalez-Lahera, A; Mosen-Ansorena, D; Blanco, FJ; Clément, K; Aron-Wisnewsky, J; Tran, A; Gual, P; García-Monzón, C; Caballería, J; Castro, ...
BIOMEDICINES
2023-02-01
Protoporphyrin IX Binds to Iron(II)-Loaded and to Zinc-Loaded Human Frataxin
Bernardo-Seisdedos, G; Schedlbauer, A; Pereira-Ortuzar, T; Mato, JM; Millet, O;
LIFE-BASEL
2023-01-01
An NMR-Based Model to Investigate the Metabolic Phenoreversion of COVID-19 Patients throughout a Longitudinal Study
Gil-Redondo, R; Conde, R; Bizkarguenaga, M; Bruzzone, C; Laín, A; González-Valle, B; Iriberri, M; Ramos-Acosta, C; Anguita, E; Lariz, JIA; Yandiola, PPE; Moran, MA; Jiménez-Mercado, ME; Egia-Mendikute, ...
METABOLITES
2022-12-01
A flow cytometry-based neutralization assay for simultaneous evaluation of blocking antibodies against SARS-CoV-2 variants
Egia-Mendikute, L; Bosch, A; Prieto-Fernández, E; Vila-Vecilla, L; Zanetti, SR; Lee, SY; Jiménez-Lasheras, B; del Río, AG; Antoñana-Vildosola, A; de Blas, A; Velasco-Beltrán, P; Serrano-Maciá, ...
FRONTIERS IN IMMUNOLOGY
2022-11-24
The use of pharmacological chaperones in rare diseases caused by reduced protein stability
Gil-Martínez, J; Bernardo-Seisdedos, G; Mato, JM; Millet, O;
PROTEOMICS
2022-10-19
ALAD Inhibition by Porphobilinogen Rationalizes the Accumulation of ?-Aminolevulinate in Acute Porphyrias br
San Juan, I; Pereira-Ortuzar, T; Cendoya, X; Laín, A; To-Figueras, J; Mateos, B; Planes, FJ; Bernardo-Seisdedos, G; Mato, JM; Millet, O;
BIOCHEMISTRY
2022-10-14
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, ...
JOURNAL OF HEPATOLOGY
2022-06-15
Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
Martínez-Arranz, I; Bruzzone, C; Noureddin, M; Gil-Redondo, R; Mincholé, I; Bizkarguenaga, M; Arretxe, E; Iruarrizaga-Lejarreta, M; Fernández-Ramos, D; Lopitz-Otsoa, F; Mayo, R; Embade, N; Newberry, ...
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, ...
ONCOGENESIS
2022-02-23
Depletion of mitochondrial methionine adenosyltransferase α1 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; Fernández-Ramos, D; Lopitz-Otsoa, F; Luque-Urbano, M; Millet, O; Mavila, N; Peng, H; Ramani, K; Gottlieb, ...
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; Schäfer, H; Spraul, M; Pompe, N; Diercks, T; Bernardo-Seisdedos, G; Mato, JM; Millet, O; Susic, D; Henry, A; El-Omar, EM; Holmes, ...
ANALYTICAL CHEMISTRY
2022-01-05