期刊
FEBS OPEN BIO
卷 7, 期 2, 页码 195-203出版社
WILEY
DOI: 10.1002/2211-5463.12175
关键词
beta alpha beta beta alpha beta folds; phenylalanine hydroxylase; regulatory domain
资金
- Fundacao para a Ciencia e a Tecnologia, Portugal [SFRH/BD/19024/2004]
- University of Bergen, Norway
- Fundação para a Ciência e a Tecnologia [SFRH/BD/19024/2004] Funding Source: FCT
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-(pep(Xa))-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 babbab ACT domain folds in the mutant.
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