蛋白质硝基化修饰位点预测工具 —— GPS-YNO2 1.0

朱雀 2022-05-15 03:36 174阅读 0赞

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   <td colspan="2"> <a href="http://www.mcponline.org/content/9/4.toc" rel="nofollow"> </a> <br><a href="mailto:lzx@mail.ustc.edu.cn" rel="nofollow">Zexian Liu</a> , Jun Cao, Qian Ma, Xinjiao Gao, <a href="mailto:renjian.sysu@gmail.com" rel="nofollow">Jian Ren</a> and <a href="mailto:xueyu@mail.hust.edu.cn" rel="nofollow">Yu Xue</a> . (2010) GPS-YNO2: Computational prediction of tyrosine nitration sites in proteins. <strong><em>Molecular BioSystems</em> </strong> (In press).</td> 
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Early after the discovery of the freely-diffusible signaling molecule and second messenger **nitric oxide** **(NO)** and its function in signal transduction within the vasculature and nervous system, it became obvious that NO also take part in cytotoxic cytotoxicity when abundantly produced by iNOS, eNOS or nNOS ([Ignarro, L.J. *et al* ., 1990][Ignarro_ L.J. _et al_ ._ 1990] ). When NO meets molecular oxygen in hydrophobic environments where these species concentrate, the nitrogen dioxide could be formed, then reactive nitrogen species are derived which leave nitration as the molecular footprints by reactions with proteins. Tyrosine nitration is a kind of covalent post-translational modifications which adds a nitro (-NO2) group onto either one of the two ortho carbons of the aromatic ring of tyrosine resides. Originally, protein tyrosine nitration was considered to take place only in vitro mediated by reactive nitrating agent such as tetranitromethane ([Sokolovsky, M. *et al* ., 1992][Sokolovsky_ M. _et al_ ._ 1992] ) and peroxynitrite ([Beckman, J.S. *et al* ., 1992][Beckman_ J.S. _et al_ ._ 1992] ; [Ischiropoulos, H. *et al* ., 1992][Ischiropoulos_ H. _et al_ ._ 1992] ). Later, seminal work by Beckman et al. and Ischiropoulos et al. etc. ([Ischiropoulos, H. *et al* ., 1992][Ischiropoulos_ H. _et al_ ._ 1992 1] ; [Beckmann, J.S. *et al* ., 1994][Beckmann_ J.S. _et al_ ._ 1994] ; [Kers, J.A. *et al* ., 2004][Kers_ J.A. _et al_ ._ 2004] ) established the concept that tyrosine nitration could be promoted in vivo, which was also suggested in a previous work ([Ohshima, H. *et al* ., 1992][Ohshima_ H. _et al_ ._ 1992] ). Although the molecular mechanism of nitration and denitration are still questioned and discussed ([Pfeiffer, S. *et al* ., 2000][Pfeiffer_ S. _et al_ ._ 2000] ; [Thomas, D.D. *et al* ., 2002][Thomas_ D.D. _et al_ ._ 2002] ; [Radi, R. *et al* ., 2004][Radi_ R. _et al_ ._ 2004] ; [van der Vliet, A. *et al* ., 2006][van der Vliet_ A. _et al_ ._ 2006] ; [Gunaydin, H. *et al* ., 2009][Gunaydin_ H. _et al_ ._ 2009] ; [Abello, N. *et al* ., 2009][Abello_ N. _et al_ ._ 2009] ), it is convinced that protein tyrosine nitration play critical roles in physiology and pathology ([Radi, R. *et al* ., 2004][Radi_ R. _et al_ ._ 2004] ; [Abello, N. *et al* ., 2009][Abello_ N. _et al_ ._ 2009] ; [Ischiropoulos, H. *et al* ., 2009][Ischiropoulos_ H. _et al_ ._ 2009] ; [Reynolds, M.R. *et al* ., 2007][Reynolds_ M.R. _et al_ ._ 2007] ; [Lu, N.H. *et al* ., 2007][Lu_ N.H. _et al_ ._ 2007] ). Many studies had attributed nitration to loss of function ([Xu, S. *et al* ., 2006][Xu_ S. _et al_ ._ 2006] ; [MacMillan-Crow, L.A. *et al* ., 1996][MacMillan-Crow_ L.A. _et al_ ._ 1996] ; [Eiserich, J.P. *et al* ., 1999][Eiserich_ J.P. _et al_ ._ 1999] ), but the concept as “gain of function” through tyrosine nitration was also raised through some reports ([Vadseth, C. *et al* ., 2004][Vadseth_ C. _et al_ ._ 2004] ; [Hodara, R. *et al* ., 2004][Hodara_ R. _et al_ ._ 2004] ; [Souza, J.M. *et al* ., 2000][Souza_ J.M. _et al_ ._ 2000] ). Though a relatively limited number of protein and a few tyrosine could be nitrated, this special post-translational modification has been assigned a lot of biological roles from being used as a biomarker oxidative stress to altering the structure and function, as well with influencing tyrosine phosphorylation. Current progresses show that protein tyrosine play important roles in species of biological process, including immunomodulation ([Nagaraj, S. *et al* ., 2007][Nagaraj_ S. _et al_ ._ 2007] ), apoptosis ([Yakovlev, V.A. *et al* ., 1992][Yakovlev_ V.A. _et al_ ._ 1992] ), cell cycle ([Kong, S.K. *et al* ., 1996][Kong_ S.K. _et al_ ._ 1996] ), cell death ([Liu, B. *et al* ., 2009][Liu_ B. _et al_ ._ 2009] ), and aging ([Drew, B. *et al* ., 2002][Drew_ B. _et al_ ._ 2002] ; [Hong, S.J. *et al* ., 2007][Hong_ S.J. _et al_ ._ 2007] ).

In this work, we manually collected **1066** experimentally indentified protein nitration sites in **554** unique proteins from scientific literature. A previously self-developed GPS (Group-based Prediction System) algorithm was employed with great improvement. We calculated the leave-one-out validation and 4-, 6-, 8-, 10-fold cross-validations to evaluate the prediction performance and system robustness. The leave-one-out validation result is accuracy (*Ac* ) of **76.51%** , sensitivity (*Sn* ) of **50.09%** , and specificity (*Sp* ) of **80.18%** . T he online service and stand-alone packages of GPS-YNO2 1.0 were implemented in JAVA 1.4.2 and freely available at: [**http://yno2.biocuckoo.org/** ][http_yno2.biocuckoo.org_] .

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***GPS-YNO2 1.0 User Interface***

[bg06.gif]: http://phossnp.biocuckoo.org/images/bg06.gif
[Ignarro_ L.J. _et al_ ._ 1990]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2188578
[Sokolovsky_ M. _et al_ ._ 1992]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5339594
[Beckman_ J.S. _et al_ ._ 1992]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1416975
[Ischiropoulos_ H. _et al_ ._ 1992]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1416974
[Ischiropoulos_ H. _et al_ ._ 1992 1]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1329657
[Beckmann_ J.S. _et al_ ._ 1994]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8192861
[Kers_ J.A. _et al_ ._ 2004]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15129284
[Ohshima_ H. _et al_ ._ 1992]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2272563
[Pfeiffer_ S. _et al_ ._ 2000]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10692434
[Thomas_ D.D. _et al_ ._ 2002]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12226478
[Radi_ R. _et al_ ._ 2004]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15020765
[van der Vliet_ A. _et al_ ._ 2006]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16934668
[Gunaydin_ H. _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19374346
[Abello_ N. _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19415921
[Ischiropoulos_ H. _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19007743
[Reynolds_ M.R. _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17542619
[Lu_ N.H. _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18232314
[Xu_ S. _et al_ ._ 2006]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16399855
[MacMillan-Crow_ L.A. _et al_ ._ 1996]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8876227
[Eiserich_ J.P. _et al_ ._ 1999]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10339593
[Vadseth_ C. _et al_ ._ 2004]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14681238
[Hodara_ R. _et al_ ._ 2004]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15364911
[Souza_ J.M. _et al_ ._ 2000]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10747881
[Nagaraj_ S. _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17603493
[Yakovlev_ V.A. _et al_ ._ 1992]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17910475
[Kong_ S.K. _et al_ ._ 1996]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8622943
[Liu_ B. _et al_ ._ 2009]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19150419
[Drew_ B. _et al_ ._ 2002]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11976187
[Hong_ S.J. _et al_ ._ 2007]: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17481840
[http_yno2.biocuckoo.org_]: http://yno2.biocuckoo.org/
[GPS-YNO2.gif]: /images/20220515/a32c139200f04541878bf3b2653067d7.png