Systemic lupus erythematosus: Possible localization of trypsin-like and metalloprotease active centers in the protein sequence of the monoclonal light chain (NGTA2-Me-pro-Tr).,Biotechnology and Applied Biochemistry

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Systemic lupus erythematosus: Possible localization of trypsin-like and metalloprotease active centers in the protein sequence of the monoclonal light chain (NGTA2-Me-pro-Tr).
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2019-11-20 , DOI: 10.1002/bab.1858
Anna M Timofeeva ₁ , Georgy A Nevinsky ₁

Affiliation

It was previously shown that several monoclonal light chains corresponding to the phagemid library of recombinant peripheral blood lymphocyte immunoglobulin light chains of patients with systemic lupus erythematosus specifically hydrolyze only myelin basic protein (MBP). Canonical enzymes usually have only one active site catalyzing some kind of chemical reaction. It was shown previously that in contrast to classical enzymes, preparations of one of the light chains (NGTA2‐Me‐pro‐Tr) showed two optimal pH values, two optimal concentrations of metal ions, and two K_m values for MBP. One protease active site of NGTA2‐Me‐pro‐Tr was trypsin like, whereas second one was metal dependent. In this article, a search for protein sequences of NGTA2‐Me‐pro‐Tr responsible for catalytic functions was carried out. We performed, for the first time, analysis of the homology of the protein sequence of NGTA2‐Me‐pro‐Tr with those of several classical Zn²⁺‐ and Ca²⁺‐dependent, as well as human serine, proteases. The analysis allowed us to identify the protein sequences of NGTA2‐Me‐pro‐Tr responsible for serine‐like activity, the binding of MBP, and chelation of metal ions and catalysis directly. The data obtained are summarized using hypothetical models of the structure of the two active centers of a very unusual light chain of antibodies (Abs). The findings obtained may be very important for understanding possible structure of active centers of very unusual light chain of Abs possessing several enzymatic activities.

中文翻译：

系统性红斑狼疮：胰蛋白酶样和金属蛋白酶活性中心可能位于单克隆轻链（NGTA2-Me-pro-Tr）的蛋白质序列中。

先前已经显示，与系统性红斑狼疮患者的重组外周血淋巴细胞免疫球蛋白轻链的噬菌粒文库相对应的几个单克隆轻链仅特异性水解髓磷脂碱性蛋白（MBP）。典型的酶通常只有一个催化某些化学反应的活性位点。先前显示，与经典酶相比，其中一条轻链（NGTA2-Me-pro-Tr）的制备显示出两个最佳pH值，两个最佳金属离子浓度和两个K _mMBP的值。NGTA2-Me-pro-Tr的一个蛋白酶活性位点是胰蛋白酶样的，而第二个是金属依赖性的。在本文中，对负责催化功能的NGTA2-Me-pro-Tr蛋白序列进行了搜索。我们首次进行了NGTA2-Me-pro-Tr蛋白序列与几种经典Zn ²⁺和Ca ²⁺蛋白序列的同源性分析以及人类丝氨酸蛋白酶。通过分析，我们可以鉴定出负责丝氨酸样活性，MBP结合以及金属离子螯合和直接催化作用的NGTA2-Me-pro-Tr蛋白序列。使用非常罕见的抗体轻链（Abs）的两个活性中心结构的假设模型汇总了获得的数据。获得的发现对于理解具有几种酶促活性的Abs的非常不寻常的轻链的活性中心的可能结构可能是非常重要的。

更新日期：2019-11-20

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