RNRdb, a curated database of the universal enzyme familyribonucleotide reductase, reveals a high level of misannotation insequences deposited to Genbank

Background: Ribonucleotide reductases (RNRs) catalyse the only known de novo pathway fordeoxyribonucleotide synthesis, and are therefore essential to DNA-based life. Whileribonucleotide reduction has a single evolutionary origin, significant differences between RNRsnevertheless exist, notably in cofactor requirements, subunit composition and allosteric regulation.These differences result in distinct operational constraints (anaerobicity, iron/oxygen dependenceand cobalamin dependence), and form the basis for the classification of RNRs into three classes.Description: In RNRdb (Ribonucleotide Reductase database), we have collated and curated allknown RNR protein sequences with the aim of providing a resource for exploration of RNRdiversity and distribution. By comparing expert manual annotations with annotations stored inGenbank, we find that significant inaccuracies exist in larger databases. To our surprise, only 23%of protein sequences included in RNRdb are correctly annotated across the key attributes of class,role and function, with 17% being incorrectly annotated across all three categories. This illustratesthe utility of specialist databases for applications where a high degree of annotation accuracy maybe important. The database houses information on annotation, distribution and diversity of RNRs,and links to solved RNR structures, and can be searched through a BLAST interface. RNRdb isaccessible through a public web interface at http://rnrdb.molbio.su.se.Conclusion: RNRdb is a specialist database that provides a reliable annotation and classificationresource for RNR proteins, as well as a tool to explore distribution patterns of RNR classes. Therecent expansion in available genome sequence data have provided us with a picture of RNRdistribution that is more complex than believed only a few years ago; our database indicates thatRNRs of all three classes are found across all three cellular domains. Moreover, we find a numberof organisms that encode all three classes