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Structural Biology Unit

Laboratory 1

The laboratory is focused on two main projects.
The first one investigates how cystathionine ß-synthase (CBS) domains regulate the activity of their target proteins upon binding of different ligands such as adenosyl groups or ions. The "CBS domain" proteins comprise a large superfamily of evolutionarily-conserved proteins which are present in all kingdoms of life. Mutations within these motifs cause several hereditary diseases in humans, such as, among others, homocystinuria, autosomic retinitis pigmentosa, myotonia congenital, idyopatic epilepsy or hypercalciuric nephrolytiasis. Thus, they can be considered as promising targets for the development of novel drugs. CBS domains are unusually abundant in archaea. Organisms such as the hyperthermophile Methanococcus jannaschii offer an excellent model for the characterization of the adenosyl binding site of these proteins.

The second project is part of the CONSOLIDER program of the Spanish Ion Channel Initiative, a multidisciplinary and cooperative initiative established to increase understanding of the structure-function relationship in ionic channels, headed by Prof. Antonio Ferrer Montiel from the University Miguel Hernández in Elche, Spain. My group is involved in the 3D structure determination of selected targets using crystallographic approaches.

Collaborations:
Dr Jan P. Kraus (University of Colorado, Denver)
Dr Vojtech Spiwok (Institute of Chemical Technology, Prague, Czech Republic)
Dr Viktor Kozich (Institute of Inherited Metabolic Disorders, Prague, Czech Republic)
Dr Dominik Müller (Department of Pediatric Nephrology, Charité Berlin, Germany).
Dr Alessio Accardi (Department of Physiology and Biophysics, Cornell University, NY, USA)
Dr Alexander Baykov(Moscow State University, Russia)
Dr Reijo Lahti (Department of Biochemistry and Food Chemistry University of Turku, Finland)
Dr Paz Sevilla Sierra, Facultad de Farmacia, UCM, Madrid
Dr José Luis Arrondo (UPV-EHU, Bilbao, Spain).
Dr Armando Albert (Instituto Rocasolano, CSIC, Madrid, Spain).
Dr Antonio Ferrer Montiel (Univ. Miguel Hernández, Elche, Spain).
Dr José Luis Neira Faleiro (Univ. Miguel Hernández, Elche, Spain).
Dr José Antonio Encinar Hidalgo (Univ. Miguel Hernández, Elche, Spain).
Dr José Andrés Hernández (UPV-EHU, Bilbao, Spain).
Dr María Luz Martínez Chantar (CIC bioGUNE, Bilbao, Spain)

Principal Investigator

Laboratory members

Publications

Lucas M, Encinar JA, Arribas EA, Oyenarte I, García IG, Kortazar D, Fernández JA, Mato JM, Martínez-Chantar ML, Martínez-Cruz LA; Binding of S-Methyl-5'-Thioadenosine and S-Adenosyl-l-Methionine to Protein MJ0100 Triggers an Open-to-Closed Conformational Change in Its CBS Motif Pair. J. Mol. Biol. 396, 3 800-20 (2010)

Martínez-Cruz LA, Encinar JA, Sevilla P, Oyenarte I, Gómez-García I, Aguado-Llera D, García-Blanco F, Gómez J, Neira JL; Nucleotide-induced conformational transitions in the CBS domain protein MJ0729 of Methanocaldococcus jannaschii. Protein Eng Des Sel. [Epub ahead of print]PMID: 20959390 (2010)

Aguado-Llera D, Oyenarte I, Martínez-Cruz LA, Neira JL; The CBS domain protein MJ0729 of Methanocaldococcus jannaschii binds DNA. FEBS Lett. [Epub ahead of print]PMID: 20934423 (2010)

Gómez-García I, Oyenarte I, Martínez-Cruz LA; The crystal structure of protein MJ1225 from Methanocaldococcus jannaschii shows strong conservation of key structural features seen in the eukaryal gamma-AMPK. J Mol Biol. 399, 1 53-70 (2010)

Martínez-Cruz LA, Encinar JA, Kortazar D, Prieto J, Goómez J, Fernández-Millán P, Lucas M, Arribas EA, Fernández JA, Martiínez-Chantar ML, Mato JM, Neira JL; The CBS Domain Protein MJ0729 of Methanocaldococcus jannaschii Is a Thermostable Protein with a pH-Dependent Self-Oligomerization. Biochemistry 48, 12 2766-2776 (2009)

Gómez García I, Kortázar D, Oyenarte I, Mato JM, Martínez-Chantar ML, Martínez-Cruz LA.; Purification, crystallization and preliminary crystallographic analysis of protein MJ1225 from Methanocaldococcus jannaschii, a putative archaeal homologue of gamma-AMPK. Acta Crystallogr Sect F Struct Biol Cryst Commun. 1, 65 813-817 (2009)

Fernández-Millán P., Kortazar D., Lucas M., Martínez-Chantar M.L., Astigarraga E., Fernández J.A., Sabas O., Albert A,. Mato J.M., Martínez-Cruz L.A.; Crystallization and preliminary crystallographic analysis of merohedrally twinned crystals of MJ0729, a CBS-domain protein from Methanococcus jannaschii. Acta Crystallogr Sect F Struct Biol Cryst Commun. 64, 605-9 (2008)

Lucas M., Kortazar D., Astigarraga E., Fernández J. A., Mato J. M., Martínez-Chantar M. L. Martínez-Cruz L. A.; Purification, crystallization and preliminary X-ray diffraction analysis of the CBS-domain pair from the Methanococcus jannaschii protein MJ0100. Acta Crystallographica, section F, 64, 10 936-941 (2008)

Rubio A., Guruceaga E., Vázquez-Chantada M., Sandoval J., Martínez-Cruz LA., Segura V., Sevilla JL., Podhorski A., Corrales FJ., Torres L., Rodríguez MS., Aillet F., Ariz U., Martínez Arrieta F., Caballería J., Martín-Duce A., Lu SC., Martínez-Chantar ML., Mato JM; Identification of a gene-pathway associated with non-alcoholic steatohepatitis. J. Hepatology 46, 4 708-718 (2007)

Martínez-Chantar ML, Vázquez M, Garnacho M, Ujue-Latasa M, Varela-Rey M, Dotor J, Santamaría M, Martínez-Cruz LA, Parada LA, Lu SC, Mato JM; S-adenosylmethionine Regulates Cytoplasmic HuR Via AMP-Activated Kinase. Gastroenterology 13, 223-232 (2006)