TY - GEN
T1 - In silico analysis of iduronate 2 sulfatase mutations in Colombian patients with Hunter Syndrome (MPSII)
AU - Galvis, Johanna
AU - González, Jannet
AU - Torrente, Daniel
AU - Velasco, Harvy
AU - Barreto, George Emilio
PY - 2014
Y1 - 2014
N2 - Hunter syndrome or Mucopolysaccharidosis II is an inherited X linked disease, caused by mutations in iduronate 2 sulfatase (IDS), enzyme which catalyzes the initial step reaction of heparan and dermatan sulfate degradation. Allelic heterogeneity in MPSII challenges genotype-phenotype correlation. With the aim of understanding the repercussion of mutations on enzyme structure-function, we performed protein modeling and docking simulations with wild and mutant forms of hIDS. Mutations were obtained from a molecular study conducted in Colombian patients. Point mutations affected substrateprotein interactions. In the case of S71N (attenuated phenotype) further experimentation is required. Novel mutants P160SfsX4, D190Pfs13X and P185GfsX2 have a severely distorted conformation. Detailed analysis of the ligand-protein interaction is also of great significance in designing molecules for treatment. This is the first report of molecular docking performed with wild and mutant forms of iduronate-2-sulfatase as a bioinformatical approach to phenotypegenotype correlation in patients with Hunter Syndrome in Colombia.
AB - Hunter syndrome or Mucopolysaccharidosis II is an inherited X linked disease, caused by mutations in iduronate 2 sulfatase (IDS), enzyme which catalyzes the initial step reaction of heparan and dermatan sulfate degradation. Allelic heterogeneity in MPSII challenges genotype-phenotype correlation. With the aim of understanding the repercussion of mutations on enzyme structure-function, we performed protein modeling and docking simulations with wild and mutant forms of hIDS. Mutations were obtained from a molecular study conducted in Colombian patients. Point mutations affected substrateprotein interactions. In the case of S71N (attenuated phenotype) further experimentation is required. Novel mutants P160SfsX4, D190Pfs13X and P185GfsX2 have a severely distorted conformation. Detailed analysis of the ligand-protein interaction is also of great significance in designing molecules for treatment. This is the first report of molecular docking performed with wild and mutant forms of iduronate-2-sulfatase as a bioinformatical approach to phenotypegenotype correlation in patients with Hunter Syndrome in Colombia.
KW - Bioinformatic analysis
KW - Molecular docking
KW - Mucopolysaccharidosis II
KW - Sulfoiduronate sulfatase
UR - http://www.scopus.com/inward/record.url?scp=84894713870&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-01568-2_30
DO - 10.1007/978-3-319-01568-2_30
M3 - Conference contribution
AN - SCOPUS:84894713870
SN - 9783319015675
T3 - Advances in Intelligent Systems and Computing
SP - 205
EP - 212
BT - Advances in Computational Biology - Proceedings of the 2nd Colombian Congress on Computational Biology and Bioinformatics CCBCOL 2013
PB - Springer Verlag
T2 - 2nd Colombian Congress on Computational Biology and Bioinformatics, CCBCOL 2013
Y2 - 25 September 2013 through 27 September 2013
ER -