Publication: Crystal structure of the flavin reductase of Acinetobacter baumannii p-hydroxyphenylacetate 3-hydroxylase (HPAH) and identification of amino acid residues underlying its regulation by aromatic ligands
8
Issued Date
2018-09-01
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ISSN
10960384
00039861
00039861
Other identifier(s)
2-s2.0-85049087126
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Mahidol University
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SCOPUS
Bibliographic Citation
Archives of Biochemistry and Biophysics. Vol.653, (2018), 24-38
Suggested Citation
Anan Yuenyao, Nopphon Petchyam, Nuntaporn Kamonsutthipaijit, Pimchai Chaiyen, Danaya Pakotiprapha Crystal structure of the flavin reductase of Acinetobacter baumannii p-hydroxyphenylacetate 3-hydroxylase (HPAH) and identification of amino acid residues underlying its regulation by aromatic ligands. Archives of Biochemistry and Biophysics. Vol.653, (2018), 24-38. doi:10.1016/j.abb.2018.06.010 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/45062
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Title
Crystal structure of the flavin reductase of Acinetobacter baumannii p-hydroxyphenylacetate 3-hydroxylase (HPAH) and identification of amino acid residues underlying its regulation by aromatic ligands
Abstract
© 2018 Elsevier Inc. The first step in the degradation of p-hydroxyphenylacetic acid (HPA) is catalyzed by the two-component enzyme p-hydroxyphenylacetate 3-hydroxylase (HPAH). The two components of Acinetobacter baumannii HPAH are known as C1 and C2, respectively. C1 is a flavin reductase that uses NADH to generate reduced flavin mononucleotide (FMNH−), which is used by C2 in the hydroxylation of HPA. Interestingly, although HPA is not directly involved in the reaction catalyzed by C1, the presence of HPA dramatically increases the FMN reduction rate. Amino acid sequence analysis revealed that C1 contains two domains: an N-terminal flavin reductase domain, and a C-terminal MarR domain. Although MarR proteins typically function as transcription regulators, the MarR domain of C1 was found to play an auto-inhibitory role. Here, we report a crystal structure of C1 and small-angle X-ray scattering (SAXS) studies that revealed that C1 undergoes a substantial conformational change in the presence of HPA, concomitant with the increase in the rate of flavin reduction. Amino acid residues that are important for HPA binding and regulation of C1 activity were identified by site-directed mutagenesis. Amino acid sequence similarity analysis revealed several as yet uncharacterized flavin reductases with N- or C-terminal fusions.