The genetics, structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease
The genetics, structure and function of the M1 aminopeptidase oxytocinase subfamily and their therapeutic potential in immune-mediated disease
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DOI：
10.1016/j.humimm.2018.11.002
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发表时间：
2019-05-01
期刊：
影响因子：
2.7
通讯作者：
Kenna, Tony J.
中科院分区：
文献类型：
--
作者：
Hanson, Aimee L.;Morton, Craig J.;Kenna, Tony J.
催产素酶亚家族的M1氨基肽酶在主要组织相容性(MHC)I类分子上呈递的多肽的加工和修剪中起着重要作用。一些大规模的基因组研究已经确定了这个酶家族的成员，最著名的是ERAP1和ERAP2，与免疫介导的疾病，包括强直性脊柱炎，牛皮癣和鸟弹头脉络膜视网膜病变。关于这些酶的遗传学以及遗传变异是如何改变它们的功能的，现在已经知道了很多，但这些变异如何导致疾病在很大程度上仍未解决。在这里，我们讨论了关于它们的结构和功能的已知情况，并强调了一些影响针对这些酶的药物开发的知识差距。
The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved. Here we discuss what is known about their structure and function and highlight some of the knowledge gaps that affect development of drugs targeting these enzymes.