L-pipecolic acid oxidase, a human enzyme essential for the degradation of L-pipecolic acid, is most similar to the monomeric sarcosine oxidases

被引:44
作者
Dodt, G
Kim, DG
Reimann, SA
Reuber, BE
McCabe, K
Gould, SJ
Mihalik, SJ
机构
[1] Kennedy Krieger Inst, Baltimore, MD 21205 USA
[2] Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany
[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA
关键词
L-amino acid oxidase; fructosyl amino acid oxidase; organelles; peroxisome targeting signal 1; peroxisomes;
D O I
10.1042/0264-6021:3450487
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
L-Pipecolic acid oxidase activity is deficient in patients with peroxisome biogenesis disorders (PBDs). Because its role, if any, in these disorders is unknown, we cloned the associated human gene and expressed its protein product. The cDNA was cloned with the use of a reverse genetics approach based on the amino acid sequence obtained from purified L-pipecolic acid oxidase from monkey. The complete cDNA, obtained by conventional library screening and 5' rapid amplification of cDNA ends, encompassed an open reading frame of 1170 bases, translating to a 390-residue protein. The translated protein terminated with the sequence AHL, a peroxisomal targeting signal 1. Indirect immunofluorescence studies showed that the protein product was expressed in human fibroblasts in a punctate pattern that co-localized with the peroxisomal enzyme catalase. A BLAST search with the amino acid sequence showed 31% identity and 53% similarity with Bacillus sp. NS-129 monomeric sarcosine oxidase, as well as similarity to all sarcosine oxidases and dehydrogenases, No similarity was found to the peroxisomal D-amino acid oxidases. The recombinant enzyme oxidized both L-pipecolic acid and sarcosine. However, PBD patients who lack the enzyme activity accumulate only L-pipecolic acid, suggesting that in humans in vivo, this enzyme is involved mainly in the degradation of L-pipecolic acid.
引用
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页码:487 / 494
页数:8
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