Published online 23 October 2008 Nucleic Acids Research, 2009, Vol. 37, Database issue D261–D266 doi:10.1093/nar/gkn680 PeroxiBase: a database with new tools for peroxidase family classification Dominique Koua1,2, Lorenzo Cerutti1, Laurent Falquet3, Christian J. A. Sigrist1, Gre´ gory Theiler2, Nicolas Hulo1 and Christophe Dunand2,* 1Swiss Institute of Bioinformatics, Swiss-Prot Group, CMU, 1 rue Michel Servet, 2Laboratory of Plant Physiology, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva 4 and 3Swiss Institute of Bioinformatics, EMBnet Group, Quartier Sorge - Baˆ timent Ge´ nopode, CH-1015 Lausanne, Switzerland Received August 15, 2008; Revised September 19, 2008; Accepted September 23, 2008 ABSTRACT Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic families, are involved in several important physiological and developmental processes. They use various peroxides as electron acceptors to catalyse a number of oxidative reac- tions and are present in almost all living organisms. We have created a peroxidase database (http:// peroxibase.isb-sib.ch) that contains all identified peroxidase-encoding sequences (about 6000 seq- uences in 940 organisms). They are distributed between 11 superfamilies and about 60 subfamilies. All the sequences have been individually annotated and checked. PeroxiBase can be consulted using six major interlink sections ‘Classes’, ‘Organisms’, ‘Cellular localisations’, ‘Inducers’, ‘Repressors’ and ‘Tissue types’. General documentation on peroxi- dases and PeroxiBase is accessible in the ‘Documents’ section containing ‘Introduction’, ‘Class description’, ‘Publications’ and ‘Links’. In addition to the database, we have developed a tool to classify peroxidases based on the PROSITE pro- file methodology. To improve their specificity and to prevent overlaps between closely related subfami- lies the profiles were built using a new strategy based on the silencing of residues. This new profile construction method and its discriminatory capacity have been tested and validated using the different peroxidase families and subfamilies present in the database. The peroxidase classification tool called PeroxiScan is accessible at the following address: http://peroxibase.isb-sib.ch/peroxiscan.php. INTRODUCTION Peroxidases are enzymes that use various peroxides (ROOH) as electron acceptors to catalyze a number of oxidative reactions. These peroxidases can be haem and non-haem proteins. They are extremely widespread and present in all living organisms. In mammals, they are implicated in biological processes as various as immune system or hormone regulation. In plants, they are involved in auxin metabolism, lignin and suberin formation, cross- linking of cell wall components, defense against pathogens or cell elongation. Humans contain more than 30 perox- idases whereas Arabidopsis thaliana has about 130 perox- idases that are grouped in 13 diﬀerent families and nine subfamilies. There has been increased interest over the last few years in the role that mammalian haem peroxidase enzymes may play in both disease prevention and human pathologies. In general, haem peroxidases tend to promote rather than inhibit oxidative damage. Some mammalian haem peroxidases use H2O2 to generate more aggressive oxidants to ﬁght intruding micro- organisms (1). Peroxidase families from prokaryotic organisms, protists and fungi have been shown to pro- mote virulence (2–5). At the biochemical level, peroxidases can be found in the same enzyme sub-subclass E.C.1.11.1.x, donor:hydro- gen-peroxide oxidoreductase (6). Currently, 15 diﬀerent EC numbers have been ascribed to peroxidase: from EC 1.11.1.1 to EC 1.11.1.16 (EC 1.11.1.4 was removed) (7). Other peroxidase families with dual enzymatic domains were classiﬁed with the following numbers: EC 1.13. 11.44, EC 1.14.99.1, EC 1.6.3.1 and EC 4.1.1.44 (7). The two independent EC numbers (1.11.1.9 and 1.11.1.12) both correspond to glutathione peroxidase and are based on the electron acceptor (hydrogen peroxide or lipid *To whom correspondence should be addressed. Tel: 0033 562 193 557; Fax: 0033 562 193 502; Email: dunand@scsv.ups-tlse.fr Present address: Christophe Dunand, SCSV-UMR5546 CNRS/UPS, 24 Chemin de Borderouge, BP 42617 Auzeville, 31326 Castanet-Tolosan, France 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.