Rawlings Neil D
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
Database (Oxford). 2009;2009:bap015. doi: 10.1093/database/bap015. Epub 2009 Nov 2.
Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides. Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins. The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors. The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic. There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates. The number of cleavages designated as 'physiological' is 13 307. The data are derived from 6095 publications. At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database. The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues. Many of the proteins described in the literature as peptidase substrates have been studied only in vitro. On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved. There are a number of cogent reasons why a site might not be conserved. Each poorly conserved site has been examined and a reason postulated. Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance. This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates. The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases.Database URL:http://merops.sanger.ac.uk.
肽酶是一类能够水解蛋白质和肽中肽键的酶。肽酶在诸如阿尔茨海默病、肿瘤和寄生虫侵袭等病理状况中发挥着重要作用，并且在病毒多聚蛋白的加工过程中也至关重要。MEROPS数据库是一个互联网资源库，其中包含有关肽酶、其底物和抑制剂的信息。该数据库现在包括了底物中切割位点的详细信息，涵盖生理和非生理、天然和合成底物。数据集中共有39118个切割位点；其中包括来自10513种不同蛋白质的34606个切割位点以及合成底物中的2677个切割位点。被指定为“生理”的切割位点数量为13307个。这些数据源自6095篇出版物。在MEROPS数据库中识别出的2415种不同肽酶中，有45%至少已知一种底物切割情况。该网站现在有三种新的展示方式：两种以标志和频率矩阵展示肽酶特异性，第三种展示每个蛋白质底物与其最密切相关的同源物之间动态生成的比对。文献中描述为肽酶底物的许多蛋白质仅在体外进行过研究。基于生理相关切割位点在物种间会保守的假设，已对每个位点在肽酶偏好方面的保守性进行了研究，并确定了一些不保守的位点。一个位点不保守可能有许多令人信服的原因。已对每个保守性较差的位点进行了研究并推测了原因。一些位点的保守性非常差，在这些位点的切割更可能是偶然的而非具有生理相关性。这个数据集可通过互联网免费获取，是用于预测肽酶底物及这些底物内切割位点的算法的有用训练集。这些数据对于抑制剂的设计以及为肽酶设计新的特异性也可能有用。数据库网址：http://merops.sanger.ac.uk
