3e39

Protein Summary

 YP_387283.1 is annotated as a Nitroreductase family protein from Desulfovibrio desulfuricans st G20 belonging to Pfam PF00881 whose members use FMN as cofactor. There are 1907 proteins in this family from 566 species with 10 unique crystal structures. PSI-BLAST shows hits with many similarly annotated proteins but there are no structures of proteins that are close in sequence. The closest structures is that of 1NOX.pdb (Ref1) with exp=2e-05 and sequence identity of ~25%. Members of this family are primarily bacterial proteins, but some eukaryotic homologs have been found in C. elegans, D. melanogaster, mouse and human (InterPro entry).

This was selected for structure detemination as a CATH mega-family target (CATH 3.40.109.10, NADH oxidase homologous superfamily).

The Conserved Domain Database indicates that this protein belongs to the Nitro_FMN_Reductase superfamily, and specifically to NADPH_oxidoreductase_1. This superfamily includes Nitro_FMN_reductase, Nitroreductase_3, Arsenite_oxidase, NfsA_FRP, Nitroreductase_2, NADPH_oxidoreductase_2, NADH_nitroreductase, Nitroreductase_1, Nitroreductase, NADH_oxidase, BluB, NfsB_like_nitroreductase, iodotyrosine_dehalogenase, Nitroreductase, NfnB, PRK10765, PRK05365, Nitroreductase_5, PRK10828 and mcbC-like_oxidoreductase.

The protein is present as a dimer in the crystal structure and crystal packing analysis suggests that this dimeric form in the solution state oligomeric form:

Superimposition of this crystal structure with that of the 1NOX (magenta) shows that the FMN is bound in the same cleft in both structures (red in this protein, grey in 1NOX), at the interface of the dimer. The low B-factors of the FMN molecule compared to that of the surrounding protein residues indicates that the cofactor is tightly bound to the protein. The conformation of the cofactor is also very similar and this is different from that usually seen in FMN flavodoxins (Ref1):

Inspection of the  FMN binding site reveals that the phosphate moiety of the FMN in this protein is stabilized by interaction with Arg14 and Arg15 (white), similar to that seen in the 1NOX structure. The Trp47 that is present near and parallel to the flavin moiety in 1NOX (blue) is not present in this protein. Instead Trp120 on the opposite site in this protein (green) appears to be within interaction distance of the bound FMN:

Another similar protein structure from this CATH and Pfam family has been solved recently at the JCSG, NP_348178.1 from Clostridium acetobutylicum, target id 390674. Interestingly, an estimation of the active site volume of this protein is ~274A3 compared to ~486A3 for NP_348178.1.

References:

1) Hecht HJ, Erdmann H, Park HJ, Sprinzl M, Schmid RD. Crystal structure of NADH oxidase from Thermus thermophilus.Nat Struct Biol. 1995 Dec;2(12):1109-14

Ligand Summary