学步园

   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
).
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
) and peroxynitrite (Beckman, J.S. 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
; Beckmann, J.S. et al
., 1994
; 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
). Although the molecular mechanism of nitration and denitration are still questioned and discussed (Pfeiffer, S. et al
., 2000
; Thomas, D.D. et al
., 2002
; Radi, R. et al
., 2004
; van der Vliet, A. et al
., 2006
; Gunaydin, H. 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
; Abello, N. et al
., 2009
; Ischiropoulos, H. et al
., 2009
; Reynolds, M.R. et al
., 2007
; Lu, N.H. et al
., 2007
). Many studies had attributed nitration to loss of function (Xu, S. et al
., 2006
;
MacMillan-Crow, L.A. et al
., 1996
; 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
; Hodara, R. et al
., 2004
; 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
), apoptosis (Yakovlev, V.A. et al
., 1992
), cell cycle (Kong, S.K. et al
., 1996
), cell death (Liu, B. et al
., 2009
), and aging (Drew, B. et al
., 2002
; 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/

.

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