Enzymology of the nematode cuticle: A potential drug target?
Enzymology of the nematode cuticle: A potential drug target?
复制标题
DOI：
10.1016/j.ijpddr.2014.05.003
复制
发表时间：
2014-08
影响因子：
4
通讯作者：
Pertab, David
中科院分区：
文献类型：
--
作者：
Page, Antony P.;Stepek, Gillian;Winter, Alan D.;Pertab, David
线虫角质层及其酶学代表了线虫控制的新靶标。角质层胶原蛋白是这一重要结构的主要结构成分。脯氨酰 4-羟化酶、二硫键和脯氨酸异构化是内质网 (ER) 内发生的关键修饰。胶原蛋白 N 端和 C 端加工以及酪氨酸交联是关键且可利用的 ER 后事件。蜕皮酶和胶原酶是寄生线虫控制抑制剂设计的主要目标。所有线虫都具有称为角质层的外部结构，这对于它们的发育和生存至关重要。该结构主要由胶原蛋白组成，胶原蛋白是从下面的皮下细胞分泌的。使用自由生活的线虫秀丽隐杆线虫进行的广泛研究表明，角质层的形成需要多种酶的活性。分泌前（用于合成胶原蛋白等蛋白质）和分泌后（用于去除先前发育阶段的角质层）都需要酶，这一过程称为换毛或脱鞘。许多寄生线虫的排泄/分泌产物含有金属蛋白酶、丝氨酸蛋白酶和半胱氨酸蛋白酶，这些蛋白酶在整个线虫门中都是保守的，并且许多蛋白酶参与蜕皮/脱鞘过程。这篇综述重点介绍了角质层形成所需的酶，重点关注分泌后蜕皮事件。在寄生线虫中鉴定出秀丽隐杆线虫酶的直系同源物，这些可能代表未来药物/疫苗开发的新候选靶标。
The nematode cuticle and its enzymology represent a novel target in nematode control. Cuticle collagens are the major structural components of this vital structure. Prolyl 4-hydroxylase, disulphide bonding and proline isomerisation are key modifications that occur within the endoplasmic reticulum (ER). Collagen N- and C-terminal processing and tyrosine cross-linking are critical and exploitable post-ER events. Moulting and collagenase enzymes are prime targets for inhibitor design in parasitic nematode control. All nematodes possess an external structure known as the cuticle, which is crucial for their development and survival. This structure is composed primarily of collagen, which is secreted from the underlying hypodermal cells. Extensive studies using the free-living nematode Caenorhabditis elegans demonstrate that formation of the cuticle requires the activity of an extensive range of enzymes. Enzymes are required both pre-secretion, for synthesis of component proteins such as collagen, and post-secretion, for removal of the previous developmental stage cuticle, in a process known as moulting or exsheathment. The excretion/secretion products of numerous parasitic nematodes contain metallo-, serine and cysteine proteases, and these proteases are conserved across the nematode phylum and many are involved in the moulting/exsheathment process. This review highlights the enzymes required for cuticle formation, with a focus on the post-secretion moulting events. Where orthologues of the C. elegans enzymes have been identified in parasitic nematodes these may represent novel candidate targets for future drug/vaccine development.
登录
查看更多内容
影响因子：
1.5
作者：
Britton, C;Murray, L
通讯作者：
Murray, L
影响因子：
4
作者：
Charlton, Wayne L.;Harel, H. Yael Meller;McPherson, Michael J.
通讯作者：
McPherson, Michael J.
影响因子：
4.8
作者：
Eschenlauer, SCP;Page, AP
通讯作者：
Page, AP
影响因子：
2.1
作者：
BRINDLEY, PJ;GAM, AA;NEVA, FA
通讯作者：
NEVA, FA
影响因子：
2.1
作者：
HONG, XQ;BOUVIER, J;MCKERROW, JH
通讯作者：
MCKERROW, JH