Latest Publications
2019
2018
2017
2014
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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Maider Bizkarguenaga Uribiarte
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Virginia Gutiérrez de Juan
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Nicanor Zalba Olaizola
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Nekane Merino
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Chiara Bruzzone
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Nieves Embade
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Beatriz González Valle
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Borja Mateos Lopez
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David Fernández Ramos
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Rubén Gil Redondo
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Tania Pereira Ortuzar
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Itxaso San Juan Quintana
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Jon Gil Martinez
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Ana Laín
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Jon Bilbao García
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Maria de los Reyes Luque Urbano
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Fernando Lopitz Otsoa
Members
Latest Publications
Multi-Omics Integration Highlights the Role of Ubiquitination in CCl4-Induced Liver Fibrosis
Mercado-Gomez, M;Lopitz-Otsoa, F;Azkargorta, M;Serrano-Maci, M;Lachiondo-Ortega, S;Goikoetxea-Usandizaga, N;Rodriguez-Agudo, R;Fernandez-Ramos, D;Bizkarguenaga, M;Gutierrez-de Juan, V;Lectez, ...
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2020-12-01
The L-alpha-Lysophosphatidylinositol/G Protein-Coupled Receptor 55 System Induces the Development of Nonalcoholic Steatosis and Steatohepatitis
Fondevila, MF;Fernandez, U;Gonzalez-Rellan, MJ;Lima, ND;Buque, X;Gonzalez-Rodriguez, A;Alonso, C;Iruarrizaga-Lejarreta, M;Delgado, TC;Varela-Rey, M;Senra, A;Garcia-Outeiral, V;Novoa, E;Iglesias, ...
HEPATOLOGY
2020-11-13
S-adenosyl-L-methionine (SAMe) halts the autoimmune response in patients with primary biliary cholangitis (PBC) via antioxidant and S-glutathionylation processes in cholangiocytes
Kilanczyk, E;Banales, JM;Wunsch, E;Barbier, O;Avila, MA;Mato, JM;Milkiewicz, M;Milkiewicz, P
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
2020-11-01
SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum
Bruzzone, C;Bizkarguenaga, M;Gil-Redondo, R;Diercks, T;Arana, E;de Vicuna, AG;Seco, M;Bosch, A;Palazon, A;San Juan, I;Lain, A;Gil-Martinez, J;Bernardo-Seisdedos, G;Fernandez-Ramos, D;Lopitz-Otsoa, ...
ISCIENCE
2020-10-23
Lysine and Arginine Protein Post-translational Modifications by Enhanced DIA Libraries: Quantification in Murine Liver Disease
Robinson, AE;Binek, A;Venkatraman, V;Searle, BC;Holewinski, RJ;Rosenberger, G;Parker, SJ;Basisty, N;Xie, XS;Lund, PJ;Saxena, G;Mato, JM;Garcia, BA;Schilling, B;Lu, SC;Van Eyk, JE
JOURNAL OF PROTEOME RESEARCH
2020-10-02
Reciprocal Regulation Between Forkhead Box M1/NF-kappa B and Methionine Adenosyltransferase 1A Drives Liver Cancer
Li, Y;Lu, LQ;Tu, J;Zhang, J;Xiong, T;Fan, W;Wang, JH;Li, M;Chen, YB;Steggerda, J;Peng, H;Chen, YH;Li, TWH;Zhou, ZG;Mato, JM;Seki, E;Liu, T;Yang, HP;Lu, SC
HEPATOLOGY
2020-10-01
Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitisviaAMPK and mTOR regulation
Fernandez-Ramos, D;Lopitz-Otsoa, F;Delacruz-Villar, L;Bilbao, J;Pagano, M;Mosca, L;Bizkarguenaga, M;Serrano-Macia, M;Azkargorta, M;Iruarrizaga-Lejarreta, M;Sot, J;Tsvirkun, D;van Liempd, SM;Goni, ...
WORLD JOURNAL OF GASTROENTEROLOGY
2020-09-14
Abnormal concentration of porphyrins in serum from COVID-19 patients
San Juan, I;Bruzzone, C;Bizkarguenaga, M;Bernardo-Seisdedos, G;Lain, A;Gil-Redondo, R;Diercks, T;Gil-Martinez, J;Urquiza, P;Arana, E;Seco, M;de Vicuna, AG;Embade, N;Mato, JM;Millet, O
BRITISH JOURNAL OF HAEMATOLOGY
2020-08-29
PINE: An Automation Tool to Extract and Visualize Protein-Centric Functional Networks
Sundararaman, N;Go, J;Robinson, AE;Mato, JM;Lu, SC;Van Eyk, JE;Venkatraman, V
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
2020-07-01
H-1 NMR-Based Urine Metabolomics Reveals Signs of Enhanced Carbon and Nitrogen Recycling in Prostate Cancer
Bruzzone, C;Loizaga-Iriarte, A;Sanchez-Mosquera, P;Gil-Redondo, R;Astobiza, I;Diercks, T;Cortazar, AR;Ugalde-Olano, A;Schafer, H;Blanco, FJ;Unda, M;Cannet, C;Spraul, M;Mato, JM;Embade, N;Carracedo, ...
JOURNAL OF PROTEOME RESEARCH
2020-06-05