PREDICTION REPORT Deciphering a Novel Thioredoxin-Like Fold Family

searching strategies have proven useful in the iden-tification of remote homologs and have facilitated both structural and functional predictions of many uncharacterized protein families. We implement these strategies to predict the structure of and to classify a previously uncharacterized cluster of or-thologs (COG3019) in the thioredoxin-like fold super-family. The results of each searching method indi-cate that thioltransferases are the closest structural family to COG3019. We substantiate this conclusion using the ab initio structure prediction method rosetta,which generates a thioredoxin-like fold simi-lar to that of the glutaredoxin-like thioltransferase (NrdH) for a COG3019 target sequence. This struc-tural model contains the thiol-redox functional mo-tif CYS-X-X-CYS in close proximity to other abso-lutely conservedCOG3019 residues, defining a novel thioredoxin-like active site that potentially binds metal ions. Finally, the rosetta-derived model struc-ture assists us in assembling a global multiple-sequence alignment of COG3019 with two other thioredoxin-like fold families, the thioltransferases and the bacterial arsenate reductases (ArsC)