RRC ID 6755
著者 Siltberg-Liberles J, Steen IH, Svebak RM, Martinez A.
タイトル The phylogeny of the aromatic amino acid hydroxylases revisited by characterizing phenylalanine hydroxylase from Dictyostelium discoideum.
ジャーナル Gene
Abstract The social amoeba Dictyostelium discoideum contains only one aromatic amino acid hydroxylase (AAAH) gene compared to at least three in metazoans. As shown in this work this gene codes for a phenylalanine hydroxylase (DictyoPAH) and phylogenetic analysis places this enzyme close to the precursor AAAHs, aiding to define the evolutionary history of the AAAH family. DictyoPAH shows significant similarities to other eukaryote PAH, but it exhibits higher activity with tetrahydrodictyopterin (DH4) than with tetrahydrobiopterin (BH4) as cofactor. DH4 is an abundant tetrahydropterin in D. discoideum while BH4 is the natural cofactor of the AAAHs in mammals. Moreover, DictyoPAH is devoid of the characteristic regulatory mechanisms of mammalian PAH such as positive cooperativity for L-Phe and activation by preincubation with the substrate. Analysis of the few active site substitutions between DictyoPAH and mammalian PAH, including mutant expression analysis, reveals potential structural determinants for allosteric regulation.
巻・号 427(1-2)
ページ 86-92
公開日 2008-12-31
DOI 10.1016/j.gene.2008.09.005
PII S0378-1119(08)00439-3
PMID 18835579
MeSH Allosteric Site Amino Acid Sequence Amino Acids / metabolism* Animals Cloning, Molecular Dictyostelium / enzymology* Kinetics Mixed Function Oxygenases / metabolism* Molecular Conformation Molecular Sequence Data Phenylalanine Hydroxylase / metabolism* Phylogeny Pterins / chemistry Sequence Homology, Amino Acid Substrate Specificity
IF 2.984
引用数 19
WOS 分野 GENETICS & HEREDITY
リソース情報
細胞性粘菌 G02489