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首页> 外文期刊>Crystallography reports >Purification, Crystallization and Crystallographic Analysis of HLA-B*15:02 Complexed with an Endogenous Peptide
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Purification, Crystallization and Crystallographic Analysis of HLA-B*15:02 Complexed with an Endogenous Peptide

机译：HLA-B * 15：02与内源肽络合的纯化，结晶和结晶分析

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The drug hypersensitivity syndrome (DHS) caused by immune response to the drug is one of the major categories of adverse drug reactions. It has been demonstrated that DHSs involve an interaction of specific major histocompatibility complex (MHC, also known as the HLA in humans) molecules, T-cell receptors, and drugs. It has been also shown that some of the most common DHS diseases are strongly associated with certain HLA allotypes. Crystallographic studies are needed to elucidate the structural bases of HLA-drug associations and their biological roles in diverse DHSs. Carbamazepine (CBZ) is an anticonvulsant and mood stabilizing drug and it could cause serious hypersensitivity reactions. A nearly 100% association of HLA-B*15:02 with CBZ-induced DHS suggests that the HLA-B*15:02 is a central participant in the pathogenesis of the disease. Here, recombinant HLA-B*15:02 was co-crystallized with an endogenous peptide. Crystals belong to the trigonal space group P1, with the unit-cell parameters a = 71.89, b = 75.81, c = 88.47 angstrom, alpha = 97.28 degrees, beta = 90.43 degrees, gamma = 92.25 degrees. Preliminary analysis indicates that the asymmetric unit contains four molecules of HLA-B*15:02 complexed with peptide and has a solvent content of about 49%.
机译：由免疫应答对药物引起的药物过敏综合征（DHS）是药物的主要类别不良反应之一。已经证明，DHSS涉及特定主要的主要组织相容性复合物（MHC，也称为人类HLA）分子，T细胞受体和药物的相互作用。还表明，一些最常见的DHS疾病与某些HLA同质型密切相关。需要晶体研究来阐明HLA - 药物关联的结构基础及其在不同DHS中的生物作用。 Carbamazepine（CBZ）是一种抗惊厥和情绪稳定药，它可能导致严重的过敏反应。具有CBZ诱导的DHS的近100％HLA-B * 15：02的关联表明HLA-B * 15：02是疾病发病机制的中央参与者。这里，重组HLA-B * 15：02用内源肽共结晶。晶体属于三角空间组P1，用单元 - 小区参数A = 71.89，B = 75.81，C = 88.47埃，α= 97.28度，β= 90.43度，γ= 92.25度。初步分析表明不对称单元含有四个HLA-B * 15：02与肽络合，溶剂含量为约49％。

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