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
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Principal Investigator
Óscar Millet
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Chiara Bruzzone
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Rubén Gil Redondo
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Beatriz González Valle
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Jon Bilbao García
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Tania Pereira Ortuzar
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Borja Mateos Lopez
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Arantza Sanz Parra
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Itxaso San Juan Quintana
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Ganeko Bernardo
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Virginia Gutiérrez de Juan
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Maider Bizkarguenaga Uribiarte
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David Fernández Ramos
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Nieves Embade
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Ana Laín
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Fernando Lopitz Otsoa
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Jon Gil Martinez
Members
Latest Publications
Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly
Simon, J;Nunez-Garcia, M;Fernandez-Tussy, P;Barbier-Torres, L;Fernandez-Ramos, D;Gomez-Santos, B;Buque, X;Lopitz-Otsoa, F;Goikoetxea-Usandizaga, N;Serrano-Macia, M;Rodriguez-Agudo, R;Bizkarguenaga, ...
CELL METABOLISM
2020-03-03
Early treatment efficacy of S-adenosylmethionine in patients with intrahepatic cholestasis: A systematic review
Noureddin, M;Sander-Struckmeier, S;Mato, JM
WORLD JOURNAL OF HEPATOLOGY
2020-02-27
Methionine Adenosyltransferase alpha 1 Is Targeted to the Mitochondrial Matrix and Interacts with Cytochrome P450 2E1 to Lower Its Expression
Murray, B;Peng, H;Barbier-Torres, L;Robinson, AE;Li, TWH;Fan, W;Tomasi, ML;Gottlieb, RA;Van Eyk, J;Lu, ZM;Mart?nez-Chantar, ML;Liangpunsakul, S;Skill, NJ;Mato, JM;Lu, SC
Hepatology (Baltimore, Md.)
2019-12-01
miR-873-5p targets mitochondrial GNMT-Complex II interface contributing to non-alcoholic fatty liver disease
Fernandez-Tussy, P;Fernandez-Ramos, D;Lopitz-Otsoa, F;Simon, J;Barbier-Torres, L;Gomez-Santos, B;Nunez-Garcia, M;Azkargorta, M;Gutierrez-de Juan, V;Serrano-Macia, M;Rodriguez-Agudo, R;Iruzubieta, ...
MOLECULAR METABOLISM
2019-11-01
Methionine adenosyltransferases in liver cancer
Murray, B;Barbier-Torres, L;Fan, W;Mato, JM;Lu, SC
WORLD JOURNAL OF GASTROENTEROLOGY
2019-08-21
Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease
Mato, JM;Alonso, C;Noureddin, M;Lu, SC
WORLD JOURNAL OF GASTROENTEROLOGY
2019-06-28
Control and regulation of S-Adenosylmethionine biosynthesis by the regulatory beta subunit and quinolone-based compounds
Panmanee, J;Bradley-Clarke, J;Mato, JM;O'Neill, PM;Antonyuk, SV;Hasnain, SS
FEBS JOURNAL
2019-06-01
Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis
Reverter, E;Lozano, JJ;Alonso, C;Berzigotti, A;Seijo, S;Turon, F;Baiges, A;Martinez-Chantar, ML;Mato, JM;Martinez-Arranz, I;La Mura, V;Hernandez-Gea, V;Bosch, J;Garcia-Pagan, JC
LIVER INTERNATIONAL
2019-04-01
NEDDylation inhibition as a new potential therapy of nonalcoholic fatty liver disease
Serrano-Macia, M;Azkargorta, M;Simon, J;Otsoa, FL;Delgado, TC;Ramos, DF;de Juan, VG;Varela-Rey, M;Goikoetxea, N;Tussy, PF;Apichueta, P;de Urturi, DS;Buque, X;Iruzubieta, P;Crespo, J;Lu, SC;Mato, ...
JOURNAL OF HEPATOLOGY
2019-04-01
Mitochondrial GNMT-complex II is recovered by miR-873-5p targeting in NAFLD
Ramos, DF;Tussy, PF;Otsoa, FL;Simon, J;Torres, LB;Santos, BG;Nunez, M;Azkargorta, M;de Juan, VG;Serrano-Macia, M;Agudo, RR;Champagne, DG;Iruzubieta, P;Anguita, J;Rincon, M;Elortza, F;Anita, ...
JOURNAL OF HEPATOLOGY
2019-04-01