Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. Export

@article{citeulike:2707333, abstract = {Hydroxylation of the aromatic amino acids phenylalanine, tyrosine and tryptophan is carried out by a family of non-heme iron and tetrahydrobiopterin (BH4) dependent enzymes, i.e. the aromatic amino acid hydroxylases (AAHs). The reactions catalyzed by these enzymes are important for biomedicine and their mutant forms in humans are associated with phenylketonuria (phenylalanine hydroxylase), Parkinson's disease and DOPA-responsive dystonia (tyrosine hydroxylase), and possibly neuropsychiatric and gastrointestinal disorders (tryptophan hydroxylase 1 and 2). We attempt to rationalize current knowledge about substrate and inhibitor specificity based on the three-dimensional structures of the enzymes and their complexes with substrates, cofactors and inhibitors. In addition, further insights on the selectivity and affinity determinants for ligand binding in the AAHs were obtained from molecular interaction field (MIF) analysis. We applied this computational structural approach to a rational analysis of structural differences at the active sites of the enzymes, a strategy that can help in the design of novel selective ligands for each AAH.}, address = {Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.}, author = {Teigen, K. and McKinney, J. A. and Haavik, J. and Mart\'{\i}nez, A.}, citeulike-article-id = {2707333}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/17305546}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=17305546}, issn = {0929-8673}, journal = {Current medicinal chemistry}, keywords = {binding, hpah, ligand, structure}, number = {4}, pages = {455--467}, posted-at = {2008-04-23 13:02:20}, priority = {2}, title = {Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/17305546}, volume = {14}, year = {2007} }

TY - JOUR ID - citeulike:2707333 L3 - citeulike-article-id:2707333 N2 - Hydroxylation of the aromatic amino acids phenylalanine, tyrosine and tryptophan is carried out by a family of non-heme iron and tetrahydrobiopterin (BH4) dependent enzymes, i.e. the aromatic amino acid hydroxylases (AAHs). The reactions catalyzed by these enzymes are important for biomedicine and their mutant forms in humans are associated with phenylketonuria (phenylalanine hydroxylase), Parkinson's disease and DOPA-responsive dystonia (tyrosine hydroxylase), and possibly neuropsychiatric and gastrointestinal disorders (tryptophan hydroxylase 1 and 2). We attempt to rationalize current knowledge about substrate and inhibitor specificity based on the three-dimensional structures of the enzymes and their complexes with substrates, cofactors and inhibitors. In addition, further insights on the selectivity and affinity determinants for ligand binding in the AAHs were obtained from molecular interaction field (MIF) analysis. We applied this computational structural approach to a rational analysis of structural differences at the active sites of the enzymes, a strategy that can help in the design of novel selective ligands for each AAH. IS - 4 JF - Current medicinal chemistry SN - 0929-8673 AD - Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. EP - 467 TI - Selectivity and affinity determinants for ligand binding to the aromatic amino acid hydroxylases. VL - 14 SP - 455 KW - binding KW - hpah KW - ligand KW - structure AU - Teigen, K AU - McKinney, JA AU - Haavik, J AU - Martínez, A PY - 2007/// UR - http://view.ncbi.nlm.nih.gov/pubmed/17305546 ER -