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编码大鼠组氨酸脱羧酶的互补DNA的表征与表达

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

作者信息

Joseph D R, Sullivan P M, Wang Y M, Kozak C, Fenstermacher D A, Behrendsen M E, Zahnow C A

机构信息

Department of Pediatrics, University of North Carolina, Chapel Hill 27599.

出版信息

Proc Natl Acad Sci U S A. 1990 Jan;87(2):733-7. doi: 10.1073/pnas.87.2.733.

DOI:10.1073/pnas.87.2.733
PMID:2300558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC53340/
Abstract

Histamine is a neurotransmitter in the central nervous system and an important modulator of gastric acid secretion, vasomotor control, inflammation, and allergic reactions. In biological systems the formation of histamine from its precursor histidine is catalyzed by the enzyme L-histidine decarboxylase (HDC; L-histidine carboxy-lyase, EC 4.1.1.22). We have cloned HDC-encoding cDNA from a fetal rat liver cDNA library (phage lambda gt11) have deduced the amino acid sequence from the nucleotide sequence. The clone was proven to be HDC cDNA by expression of active recombinant enzyme in COS cells and by chromosomal mapping. The cDNA encodes a protein of Mr 73,450 (655 amino acid residues). The discrepancy between this molecular weight and the size of the purified fetal liver protein subunits [Taguchi, Y., Watanabe, T., Kubota, H., Hayashi, H. & Wada, H. (1984) J. Biol. Chem. 259, 5214-5221] (Mr = 54,000) suggests that HDC may be posttranslationally processed. The 469 amino acid residues from the amino-terminal portion of the protein share 50% identity with rat and Drosophila L-dopa decarboxylases and much less homology with other characterized amino acid decarboxylases.

摘要

组胺是中枢神经系统中的一种神经递质,也是胃酸分泌、血管舒缩控制、炎症和过敏反应的重要调节因子。在生物系统中,组胺由其前体组氨酸形成的过程由L-组氨酸脱羧酶(HDC;L-组氨酸羧基裂解酶,EC 4.1.1.22)催化。我们从胎鼠肝脏cDNA文库(噬菌体λgt11)中克隆了编码HDC的cDNA,并从核苷酸序列推导了氨基酸序列。通过在COS细胞中表达活性重组酶以及染色体定位,证明该克隆为HDC cDNA。该cDNA编码一个Mr为73,450(655个氨基酸残基)的蛋白质。此分子量与纯化的胎肝蛋白质亚基[田口洋、渡边彻、久保田浩、林秀夫、和田博(1984年)《生物化学杂志》259卷,5214 - 5221页](Mr = 54,000)的大小之间的差异表明,HDC可能在翻译后进行了加工处理。该蛋白质氨基末端部分的469个氨基酸残基与大鼠和果蝇的L-多巴脱羧酶有50%的同一性,与其他已鉴定的氨基酸脱羧酶的同源性则低得多。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32fe/53340/ea9eec5285e7/pnas01027-0241-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32fe/53340/ea9eec5285e7/pnas01027-0241-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32fe/53340/ea9eec5285e7/pnas01027-0241-a.jpg

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本文引用的文献

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The effects of protease inhibitors on histidine decarboxylase activities and assay of enzyme in various rat tissues.蛋白酶抑制剂对大鼠各种组织中组氨酸脱羧酶活性的影响及酶的测定
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Genome Possesses a Complete Melatonin Biosynthesis Pathway Differentially Expressed under the Influence of the Phytopathogenic Bacterium, Liberibacter asiaticus.基因组拥有一条完整的褪黑素生物合成途径,该途径在植物致病细菌亚洲韧皮杆菌的影响下差异表达。
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The C-terminus of rat L-histidine decarboxylase specifically inhibits enzymic activity and disrupts pyridoxal phosphate-dependent interactions with L-histidine substrate analogues.大鼠L-组氨酸脱羧酶的C末端特异性抑制酶活性,并破坏与L-组氨酸底物类似物的磷酸吡哆醛依赖性相互作用。
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