Prediction of reversibly oxidized protein cysteine thiols using protein structure properties
- 1 March 2008
- journal article
- Published by Wiley in Protein Science
- Vol. 17 (3), 473-481
- https://doi.org/10.1110/ps.073252408
Abstract
Protein cysteine thiols can be divided into four groups based on their reactivities: those that form permanent structural disulfide bonds, those that coordinate with metals, those that remain in the reduced state, and those that are susceptible to reversible oxidation. Physicochemical parameters of oxidation-susceptible protein thiols were organized into a database named the Balanced Oxidation Susceptible Cysteine Thiol Database (BALOSCTdb). BALOSCTdb contains 161 cysteine thiols that undergo reversible oxidation and 161 cysteine thiols that are not susceptible to oxidation. Each cysteine was represented by a set of 12 parameters, one of which was a label (1/0) to indicate whether its thiol moiety is susceptible to oxidation. A computer program (the C4.5 decision tree classifier re-implemented as the J48 classifier) segregated cysteines into oxidation-susceptible and oxidation-non-susceptible classes. The classifier selected three parameters critical for prediction of thiol oxidation susceptibility: (1) distance to the nearest cysteine sulfur atom, (2) solvent accessibility, and (3) pKa. The classifier was optimized to correctly predict 136 of the 161 cysteine thiols susceptible to oxidation. Leave-one-out cross-validation analysis showed that the percent of correctly classified cysteines was 80.1% and that 16.1% of the oxidation-susceptible cysteine thiols were incorrectly classified. The algorithm developed from these parameters, named the Cysteine Oxidation Prediction Algorithm (COPA), is presented here. COPA prediction of oxidation-susceptible sites can be utilized to locate protein cysteines susceptible to redox-mediated regulation and identify possible enzyme catalytic sites with reactive cysteine thiols.Keywords
This publication has 42 references indexed in Scilit:
- ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain architectures but differing substrate–partner associationsThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.Biochemistry and Cell Biology, 2006
- DISULFIND: a disulfide bonding state and cysteine connectivity prediction serverNucleic Acids Research, 2006
- DiANNA 1.1: an extension of the DiANNA web server for ternary cysteine classificationNucleic Acids Research, 2006
- Assignment of the Zinc Ligands in RsrA, a Redox-Sensing ZAS Protein from Streptomyces coelicolorBiochemistry, 2006
- S‐glutathiolation by peroxynitrite of p21ras at cysteine‐118 mediates its direct activation and downstream signaling in endothelial cellsThe FASEB Journal, 2006
- Very fast empirical prediction and rationalization of protein pKa valuesProteins-Structure Function and Bioinformatics, 2005
- Protein Disulfide Bond Formation in ProkaryotesAnnual Review of Biochemistry, 2003
- Copper uptake is required for pyrrolidine dithiocarbamate-mediated oxidation and protein level increase of p53 in cellsBiochemical Journal, 2002
- Basic local alignment search toolJournal of Molecular Biology, 1990
- The interpretation of protein structures: Estimation of static accessibilityJournal of Molecular Biology, 1971