Crystal structure of a novel viral protease with a serine/lysine catalytic dyad mechanism
Crystal structure of a novel viral protease with a serine/lysine catalytic dyad mechanism
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DOI：
10.1016/j.jmb.2006.02.045
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发表时间：
2006-05-19
影响因子：
5.6
通讯作者：
Paetzel, Mark
中科院分区：
文献类型：
--
作者：
Feldman, Anat R.;Lee, Jaeyong;Paetzel, Mark
斑点蛇头病毒(BSNV)是一种水生禽类病毒，编码一种多蛋白(NH2-pVP2-X-VP4-VP3-COOH)，通过自身的蛋白水解酶(VP4)进行加工，释放自身和病毒蛋白pVP2、X和VP3。蛋白pVP2被VP4进一步加工，产生衣壳蛋白VP2和四个结构肽。本文报道了BSNV VP4蛋白水解酶的晶体结构，它的活性部位有一个催化的丝氨酸/赖氨酸二聚体。这是伯纳病毒蛋白水解酶的第一个晶体结构，也是第一个在其催化机制中使用赖氨酸通用碱基的病毒蛋白酶的晶体结构。VP4底物结合位点的拓扑结构与酶的底物特异性和底物剪切键表面的亲核攻击是一致的。尽管序列同源性较低，但VP4在活性位点上与信号肽、LexA和Lon等其他特征的Ser/Lys蛋白水解酶有相似之处。综上所述，VP4的结构提供了对最近表征的利用赖氨酸通用碱基的丝氨酸蛋白酶家族的机制的洞察，并揭示了抗病毒治疗的潜在靶点的结构，特别是对其他相关和经济上重要的病毒，如家禽传染性法氏囊病病毒和水产养殖中的传染性胰腺坏死病毒。(C)2006爱思唯尔有限公司。保留所有权利。
The blotched snakehead virus (BSNV), an aquatic birnavirus, encodes a polyprotein (NH2-pVP2-X-VP4-VP3-COOH) that is processed through the proteolytic activity of its own protease (VP4) to liberate itself and the viral proteins pVP2, X and VP3. The protein pVP2 is further processed by VP4 to give rise to the capsid protein VP2 and four structural peptides. We report here the crystal structure of a VP4 protease from BSNV, which displays a catalytic serine/lysine dyad in its active site. This is the first crystal structure of a birnavirus protease and the first crystal structure of a viral protease that utilizes a lysine general base in its catalytic mechanism. The topology of the VP4 substrate binding site is consistent with the enzymes substrate specificity and a nucleophilic attack from the si-face of the substrates scissile bond. Despite low levels of sequence identity, VP4 shows similarities in its active site to other characterized Ser/Lys proteases such as signal peptidase, LexA protease and Lon protease. Together, the structure of VP4 provides insights into the mechanism of a recently characterized clan of serine proteases that utilize a lysine general base and reveals the structure of potential targets for antiviral therapy, especially for other related and economically important viruses, such as infectious bursal disease virus in poultry and infectious pancreatic necrosis virus in aquaculture. (c) 2006 Elsevier Ltd. All rights reserved.