Sobolev B.N., Filimonov D.A., Lagunin A.A., Zakharov A.V., Koborova O.N, Kel A., Poroikov V.V.
- BMC Bioinformatics , 2010
Background: The knowledge about proteins with specific interaction capacity to the protein partners is very important for the modeling of cell signaling networks. However, the experimentally-derived data are sufficiently not
complete for the...
Background: The knowledge about proteins with specific interaction capacity to the protein partners is very important for the modeling of cell signaling networks. However, the experimentally-derived data are sufficiently not
complete for the reconstruction of signaling pathways. This problem can be solved by the network enrichment with predicted protein interactions. The previously published in silico method PAAS was applied for prediction of
interactions between protein kinases and their substrates.
Results: We used the method for recognition of the protein classes defined by the interaction with the same protein partners. 1021 protein kinase substrates classified by 45 kinases were extracted from the Phospho.ELM database and
used as a training set. The reasonable accuracy of prediction calculated by leave-one-out cross validation procedure was observed in the majority of kinase-specificity classes. The random multiple splitting of the studied set onto the test and training set had also led to satisfactory results. The kinase substrate specificity for 186 proteins extracted from
TRANSPATH® database was predicted by PAAS method. Several kinase-substrate interactions described in this database were correctly predicted. Using the previously developed ExPlain™ system for the reconstruction of signal transduction
pathways, we showed that addition of the newly predicted interactions enabled us to find the possible path between signal trigger, TNF-alpha, and its target genes in the cell.
Conclusions: It was shown that the predictions of protein kinase substrates by PAAS were suitable for the enrichment of signaling pathway networks and identification of the novel signaling pathways. The on-line version of PAAS for
prediction of protein kinase substrates is freely available at http://www.ibmc.msk.ru/PAAS/. BMC Bioinformatics, 2010, 11: 313.
Sokolov AV, Ageeva KV, Pulina MO, Zakharova ET, Vasilyev VB.
- Biometals , 2009
In our previous report we first described a complex between lactoferrin (Lf) and ceruloplasmin (Cp) with K (d) ~ 1.8 muM. The presence of this complex in colostrum that never contains more than 0.3 muM Cp questions the reliability of K (d) value....
In our previous report we first described a complex between lactoferrin (Lf) and ceruloplasmin (Cp) with K (d) ~ 1.8 muM. The presence of this complex in colostrum that never contains more than 0.3 muM Cp questions the reliability of K (d) value. We carefully studied Lf binding to Cp and investigated the enzymatic activity of the latter in the presence of Lf, which allowed obtaining a new value for K (d) of Cp-Lf complex. Lf interacting with Cp changes its oxidizing activity with various substrates, such as Fe(2+), o-dianisidine (o-DA), p-phenylenediamine (p-PD) and dihydroxyphenylalanine (DOPA). The presence of at least two binding sites for Lf in Cp molecule is deduced from comparison of substrates' oxidation kinetics with and without Lf. When Lf binds to the first site affinity of Cp to Fe(2+) and to o-DA increases, but it decreases towards DOPA and remains unchanged towards p-PD. Oxidation rate of Fe(2+) grows, while that of o-DA, p-PD and DOPA goes down. Subsequent Lf binding to the second center has no effect on iron oxidation, hampers DOPA and o-DA oxidation, and reduces affinity towards p-PD. Scatchard plot for Lf sorbing to Cp-Sepharose allowed estimating K (d) for Lf binding to high-affinity (~13.4 nM) and low-affinity (~211 nM) sites. The observed effect of Lf on ferroxidase activity of Cp is likely to have physiological implications. Sokolov AV, Ageeva KV, Pulina MO, Zakharova ET, Vasilyev VB. (2009) Effect of lactoferrin on oxidative features of ceruloplasmin.// Biometals, V. 22, P. 521-529.
