282456 Exploring the Relationship Between Helicobacter Pylori's Caga Sequence and Affinity with Host's Receptors: A Proposal for Molecular Diagnostic Tools

Wednesday, October 31, 2012: 10:35 AM
Pennsylvania East (Westin )
Paula Andrea Delgado Pinzón1, Carlos Alberto Jaramillo Henao2, María del Pilar Delgado Perafán2, Natalia Melisa Peñaranda Fajardo2, Nathalia Garces Ferrreira3, Harold Enrique Castro Barrera3 and Andrés Fernando González Barrios1, (1)Chemical Engineering, Universidad de los Andes, Bogotá, Colombia, (2)Biological Sciences , Universidad de los Andes, Bogotá, Colombia, (3)Systems and Computing Engineering , Universidad de los Andes, Bogotá, Colombia

Helicobacter pylori is a human pathogen reported to be present in nearly 50% of world’s population1,2. Moreover the virulence of the strain is one of the major determinants for disease developing among infected people. One of the major factors associated to H. pylori virulence is the cytotoxin associated gene A (cagA) which encodes the CagA protein3,4. This protein is injected directly from the microorganism through type 4 secretion system (T4SS) to gastrointestinal epithelial cells, where disrupts the cellular signaling mechanism5. It is known that CagA has a 5’ region highly conserve while 3’ region is variable due to the presence of different types and/or numbers of repeat sequences which contains an EPIYA motif location where the phosphorylation of the protein takes place2,6. These differences in sequence may have a relationship with the affinity of CagA with host’s receptors and hence with the pathogenicity of H. pylori. Here in this work we obtained several sequences of different Colombian CagA strains and determine the tertiary structure using I-Tasser7 server based on multiple threading complemented with Replica Exchange Dynamics technique8 using opportunistic Cloud Infraestructure. Then, these structures were docked9,10 with different receptors including SCHP-2 and Src. Free energy calculations were correlated with the pathogenicity of the strains which were previously categorized by its pathogenicity level (cancer, chronic ulcer, chronic gastritis etc) in order to determine a potential tool for molecular diagnostics.


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