Estudio de sistemas biológicos asociados a la membrana celular mediante una aproximación computacional

Más allá de mantener la integridad celular y actuar como primera barrera de protección, la membrana es lugar de residencia para aproximadamente el 30% de las proteínas en nuestro genoma. Además de estas proteínas, multitud de moléculas se integran o interaccionan con la membrana de modo transitorio para desarrollar su función fisiológica. Por tanto, la membrana no es sólo un soporte físico, sino que juega un papel fundamental en la regulación funcional de multitud de moléculas. Repasaremos los avances obtenidos en este área utilizando técnicas de biología computacional, y cómo estos han sido imprescindibles en mi investigación de moléculas asociadas a membrana tan distintas como los péptidos antimicrobianos y los receptores de membrana acoplados a proteínas G.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Conferencia patrocinada con los fondos para conferenciantes del Departamento de Biología Molecular y Bioquímica de la UM

The noni anthraquinone damnacanthal is a multi-kinase inhibitor with potent anti-angiogenic effects

Este es el manuscrito que fue aceptado y que finalmente se publicó en Cancer Letters con el DOI: 10.1016/j.canlet.2016.10.037The natural bioactive compound damnacanthal inhibits several tyrosine kinases. Herein, we show that -in fact- damancanthal is a multi kinase inhibitor. A docking and molecular dynamics simulation approach allows getting further insight on the inhibitory effect of damnacanthal on three different kinases: vascular endothelial growth factor receptor-2, c-Met and focal adhesion kinase. Several of the kinases targeted and inhibited by damnacanthal are involved in angiogenesis. Ex vivo and in vivo experiments clearly demonstrate that, indeed, damnacanthal is a very potent inhibitor of angiogenesis. A number of in vitro assays contribute to determine the specific effects of damnacanthal on each of the steps of the angiogenic process, including inhibition of tubulogenesis, endothelial cell proliferation, survival, migration and production of extracellular matrix remodeling enzyme. Taken altogether, these results suggest that damancanthal could have potential interest for the treatment of cancer and other angiogenesisdependent diseases.Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). JAGV had the financial support of Vicerrectorado de Investigación y Transferencia (University of Málaga, Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

AMMO-Prot: amine system project 3D-model finder

BACKGROUND: Amines are biogenic amino acid derivatives, which play pleiotropic and very important yet complex roles in animal physiology. For many other relevant biomolecules, biochemical and molecular data are being accumulated, which need to be integrated in order to be effective in the advance of biological knowledge in the field. For this purpose, a multidisciplinary group has started an ontology-based system named the Amine System Project (ASP) for which amine-related information is the validation bench. RESULTS: In this paper, we describe the Ontology-Based Mediator developed in the Amine System Project (http://asp.uma.es) using the infrastructure of Semantic Directories, and how this system has been used to solve a case related to amine metabolism-related protein structures. CONCLUSIONS: This infrastructure is used to publish and manage not only ontologies and their relationships, but also metadata relating to the resources committed with the ontologies. The system developed is available at http://asp.uma.es/WebMediator

Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the "histamine system" with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.The experimental work carried out by our group is supported by grants PID2019-105010RB I00 (Spanish Ministry of Science, Innovation and Universities), and UMA18-FEDERJA-220 (Andalu sian Government and FEDER) and funds from group BIO 267 (Andalusian Government). The “CIBER de Enfermedades Raras” and “CIBER de Fisiopatología de la Obesidad y la Nutrición” are an initiative from the ISCIII (Spain).Ye

Uso de un compueso de fórmula (I) para la fabricación de un medicamento destinado al tratamiento de la enfermedad de Gaucher, composición farmacéutica, un compuesto de fórmula (Ib) y procedimiento de obtención

Uso de un compuesto de fórmula (I) para la fabricación de un medicamento destinado al tratamiento de la enfermedad de Gaucher en un sujeto humano, una composición farmacéutica que comprende un compuesto de fórmula (I), compuestos de fórmula (Ib) y su procedimiento de obtención.Peer reviewedCentro de Investigación Biomédica en Red de Enfermedades Raras, Instituto Aragonés de Ciencias de la Salud, Universidad de Zaragoza, Universidad de Málaga, Consejo Superior de Investigaciones Científicas (España), Universidad de SevillaA1 Solicitud de patente con informe sobre el estado de la técnic

Bicyclic Derivatives of L-Idonojirimycin as Pharmacological Chaperones for Neuronopathic Forms of Gaucher Disease

New human β-glucocerebrosidase (GCase) ligands with rigid 1,6-anhydro-β-L-idonojirimycin cores have been designed with the aid of molecular modeling. Efficient pharmacological chaperones for the L444P (trafficking-incompetent) mutant GCase enzyme associated with type 2 and 3 Gaucher disease (GD) were identified.Peer Reviewe

Two metadata ontologies provide the required elements to keep the metadata about registered ontologies (OMV: Ontology Metadata Vocabulary) and data sources (SDMO: Semantic Directory Metadata Ontology)

<p><b>Copyright information:</b></p><p>Taken from "AMMO-Prot: amine system project 3D-model finder"</p><p>http://www.biomedcentral.com/1471-2105/9/S4/S3</p><p>BMC Bioinformatics 2008;9(Suppl 4):S5-S5.</p><p>Published online 25 Apr 2008</p><p>PMCID:PMC2367632.</p><p></p

Molecular dynamics simulations of Glu228Ala SNP in TRAILR-1.

<p>A and C corresponds to the superimposed structures of the 50s and 90s loops respectively in the initial (green) and final (orange) model of the <b>wild type</b> of TRAILR-1 (Glutamatic acid at position 228). B and D corresponds to the superimposed structures of the loops in the initial (green) and final (brown) model of the <b>mutant type</b> of TRAILR-1 (Alanine at position 228).</p

TRAILR-1 expression levels among Responders and Non Responders to IFN beta therapy, in different PBMC subsets.

<p>Expression level is represented as relative expression compared to the reference gene GAPDH, using the ΔΔCt method. TRAILR-1 expression levels between responder and non responder patients to IFN beta therapy in each of the assessed cell subsets were compared by a Mann Whitney test.</p