dc.contributor.author | Leandro, João | en_US |
dc.contributor.author | Saraste, Jaakko | en_US |
dc.contributor.author | Leandro, Paula | en_US |
dc.contributor.author | Flatmark, Torgeir | en_US |
dc.date.accessioned | 2018-09-06T11:11:30Z | |
dc.date.available | 2018-09-06T11:11:30Z | |
dc.date.issued | 2017-02 | |
dc.Published | Leandro J, Saraste J, Leandro P, Flatmark T. PKU mutation p.G46S prevents the stereospecific binding of l-phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain. FEBS Open Bio. 2017;7(2):195-203 | eng |
dc.identifier.issn | 2211-5463 | |
dc.identifier.uri | https://hdl.handle.net/1956/18416 | |
dc.description.abstract | Mammalian phenylalanine hydroxylase (PAH) has a potential allosteric regulatory binding site for l‐phenylalanine (l‐Phe), in addition to its catalytic site. This arrangement is supported by a crystal structure of a homodimeric truncated form of the regulatory domain of human PAH (hPAH‐RD1–118/19–118) [Patel D et al. (2016) Sci Rep doi: 10.1038/srep23748]. In this study, a fusion protein of the domain (MBP‐(pepXa)‐hPAH‐RD1–120) was overexpressed and recovered in a metastable and soluble state, which allowed the isolation of a dimeric and a monomeric fusion protein. When cleaved from MBP, hPAH‐RD forms aggregates which are stereospecifically inhibited by l‐Phe (> 95%) at low physiological concentrations. Aggregation of the cleaved dimer of the mutant form hPAH‐G46S‐RD was not inhibited by l‐Phe, which is compatible with structurally/conformationally changed βαββαβ ACT domain folds in the mutant. | en_US |
dc.language.iso | eng | eng |
dc.publisher | FEBS Press | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | eng |
dc.subject | βαββαβ folds | eng |
dc.subject | phenylalanine hydroxylase | eng |
dc.subject | regulatory domain | eng |
dc.title | PKU mutation p.G46S prevents the stereospecific binding of l-phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2018-03-05T13:28:07Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2016 The Author(s) | |
dc.identifier.doi | https://doi.org/10.1002/2211-5463.12175 | |
dc.identifier.cristin | 1480103 | |
dc.source.journal | FEBS Open Bio | |