The cyclooxygenases.

The cyclooxygenases.
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DOI:
10.1186/gb-2004-5-9-241
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发表时间:
2004
期刊:
影响因子:
12.3
通讯作者:
Simmons DL
Simmons DL
中科院分区:
生物学1区
文献类型:
--
作者:
Chandrasekharan NV;Simmons DL

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环氧合酶(COX)催化前列腺素合成的限速步骤,前列腺素是一种生物活性化合物,涉及发烧和疼痛敏感等过程,是阿司匹林类药物的靶标。在哺乳动物中,这两个COX基因编码一个结构性同工酶(COX-1)和一个诱导性同工酶(COX-2)。环氧合酶(COX)催化前列腺素合成的限速步骤,前列腺素是一种生物活性化合物,涉及发烧和疼痛敏感等过程,是阿司匹林类药物的靶标。COX基因已经从珊瑚、被囊动物和脊椎动物中克隆出来,在所有发现COX基因的门中,都有两个基因编码两个COX同工酶;目前尚不清楚这些基因是来自早期的单复制事件,还是来自进化过程中的多个独立复制。COX基因的内含子-外显子排列在脊椎动物中是完全保守的,在所有物种中都是保守的。外显子边界主要定义了编码蛋白质的四个功能结构域:氨基末端疏水信号肽、二聚化结构域、膜结合域和催化域。每种酶的催化结构域都包含不同的过氧化物酶和环氧合酶活性部位;Coxs被归类为髓过氧化物酶家族的成员。所有的Cox都是同源二聚体和单调的膜蛋白(只插入膜的一个小叶中),它们似乎定位于内质网的管腔膜,在那里它们被N-糖基化。在哺乳动物中,这两个COX基因编码一个结构性同工酶(COX-1)和一个诱导性同工酶(COX-2),两者都具有重要的药理学意义。
Cyclooxygenases (COXs) catalyze the rate-limiting step in the production of prostaglandins, bioactive compounds involved in processes such as fever and sensitivity to pain, and are the target of aspirin-like drugs. In mammals, the two COX genes encode a constitutive isoenzyme (COX-1) and an inducible isoenzyme (COX-2). Cyclooxygenases (COXs) catalyze the rate-limiting step in the production of prostaglandins, bioactive compounds involved in processes such as fever and sensitivity to pain, and are the target of aspirin-like drugs. COX genes have been cloned from coral, tunicates and vertebrates, and in all the phyla where they are found, there are two genes encoding two COX isoenzymes; it is unclear whether these genes arose from an early single duplication event or from multiple independent duplications in evolution. The intron-exon arrangement of COX genes is completely conserved in vertebrates and mostly conserved in all species. Exon boundaries largely define the four functional domains of the encoded protein: the amino-terminal hydrophobic signal peptide, the dimerization domain, the membrane-binding domain, and the catalytic domain. The catalytic domain of each enzyme contains distinct peroxidase and cyclooxygenase active sites; COXs are classified as members of the myeloperoxidase family. All COXs are homodimers and monotopic membrane proteins (inserted into only one leaflet of the membrane), and they appear to be targeted to the lumenal membrane of the endoplasmic reticulum, where they are N-glycosylated. In mammals, the two COX genes encode a constitutive isoenzyme (COX-1) and an inducible isoenzyme (COX-2); both are of significant pharmacological importance.
DOI: 10.1038/384644a0
发表时间: 1996-12-19
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Stallings, WC
DOI: 10.1073/pnas.1835863100
发表时间: 2003-11-11
影响因子: 11.1
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发表时间: 2002-08-01
影响因子: 2.9
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DOI: 10.1038/nsb1196-927
发表时间: 1996-11-01
期刊: NATURE STRUCTURAL BIOLOGY
影响因子: --
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