Summary: Nitroreductase family
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Nitroreductase Edit Wikipedia article
| Nitroreductase | |||||||||||
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| Identifiers | |||||||||||
| Symbol | Nitroreductase | ||||||||||
| Pfam | PF00881 | ||||||||||
| InterPro | IPR000415 | ||||||||||
| CDD | cd02062 | ||||||||||
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Nitroreductases are a family of evolutionarily related proteins involved in the reduction of nitrogen-containing compounds, including those containing the nitro functional group. Members of this family utilise flavin mononucleotide as a cofactor and are often found to be homodimers.[1][2]
Members of this family include oxygen-insensitive NAD(P)H nitroreductase (flavin mononucleotide-dependent nitroreductase) (6,7-dihydropteridine reductase) (EC 1.5.1.34) and NADH dehydrogenase (EC 1.6.99.3). A number of these proteins are described as oxidoreductases. They are primarily found in bacterial lineages though a number of eukaryotic homologs have been identified: C. elegans P34273, D. melanogaster Q8T3Q0, Q9VTE7, mouse Q9DCX8 and human O75989. This protein is not found in photosynthetic eukaryotes. The sequences containing this entry in photosynthetic organisms are possible false positives.
The nitroreductase of Enterobacter cloacae was identified by Bryant and Deluca[3] in a strain isolated from a munitions facility, on the basis of its ability to metabolize TNT (trinitrotoluene). Since then many homologues have been identified and the family is now known to include members in diverse organisms, that catalize diverse reactions. The iodotyrosine deiodenase of mammals is a dehalogenase, the BluB of Sinorhizobium meliloti cannibalizes the bound flavin mononucleotideto furnish a critical intermediate in vitamin B12 biosynthesis.
Crystal structures of the E. cloacae and E. coli enzymes have been published with a variety of substrates and analogues bound.
An example of a potential cold-active enzyme for prodrug therapy was described using a cold-active nitroreductase, Ssap-NtrB[4] (Çelik and Yetis, 2012). Despite Ssap-NtrB derived from a mesophilic bacterium, it showed optimal activity at 20°C against cancer prodrugs. Authors comment that the cold-activity of this novel enzyme will be useful for therapies in combination with crymotherapy, exposing the target tissue to low temperatures in order to trigger the enzyme activity to activate the drug only where is required. Moreover, the enzyme could also be used for bioremediation of compounds of explosive and volatile nature in regions where high activity at low temperatures is needed.
Subfamilies
Human proteins containing this domain
IYD;
References
- ^ Hecht HJ, Erdmann H, Park HJ, Sprinzl M, Schmid RD (December 1995). "Crystal structure of NADH oxidase from Thermus thermophilus". Nat. Struct. Biol. 2 (12): 1109–14. doi:10.1038/nsb1295-1109. PMID 8846223.
- ^ de Oliveira IM, Henriques JA, Bonatto D (April 2007). "In silico identification of a new group of specific bacterial and fungal nitroreductases-like proteins". Biochem. Biophys. Res. Commun. 355 (4): 919–25. doi:10.1016/j.bbrc.2007.02.049. PMID 17331467.
- ^ Bryant, C.; DeLuca, M. (1991-03-05). "Purification and characterization of an oxygen-insensitive NAD(P)H nitroreductase from Enterobacter cloacae". Journal of Biological Chemistry. 266 (7): 4119–4125. ISSN 0021-9258. PMID 1999405.
- ^ Çelik, Ayhan; Yetiş, Gülden (2012-06-01). "An unusually cold active nitroreductase for prodrug activations". Bioorganic & Medicinal Chemistry. 20 (11): 3540–3550. doi:10.1016/j.bmc.2012.04.004. PMID 22546205.
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Nitroreductase family Provide feedback
The nitroreductase family comprises a group of FMN- or FAD-dependent and NAD(P)H-dependent enzymes able to metabolize nitrosubstituted compounds.
Literature references
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Hecht HJ, Erdmann H, Park HJ, Sprinzl M, Schmid RD , Nat Struct Biol 1995;2:1109-1114.: Crystal structure of NADH oxidase from Thermus thermophilus. PUBMED:8846223 EPMC:8846223
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de Oliveira IM, Henriques JA, Bonatto D; , Biochem Biophys Res Commun. 2007;355:919-925.: In silico identification of a new group of specific bacterial and fungal nitroreductases-like proteins. PUBMED:17331467 EPMC:17331467
Internal database links
| SCOOP: | TM1586_NiRdase |
| Similarity to PfamA using HHSearch: | TM1586_NiRdase TM1586_NiRdase |
External database links
| HOMSTRAD: | Nitroreductase |
| SCOP: | 1nox |
This tab holds annotation information from the InterPro database.
InterPro entry IPR029479
The entry represents a domain found in a group of FMN- or FAD-dependent and NAD(P)H-dependent nitroreductases that are able to metabolise nitrosubstituted compounds [PUBMED:17331467, PUBMED:8846223].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan FMN-dep-NRtase (CL0529), which has the following description:
This superfamily is involved in the reduction of nitrogen containing compounds. Members of this family utilise FMN as a cofactor and are often found to be homodimers. Possible characteristics include Oxygen-insensitive NAD(P)H nitroreductase (FMN-dependent nitroreductase) (Dihydropteridine reductase) and NADH dehydrogenase. A number of the proteins are described as oxidoreductases. They are primarily found in bacterial lineages though a number of eukaryotic homologues have been identified: Caenorhabditis elegans, Drosophila melanogaster, mouse and human. These protein are not found in photosynthetic eukaryotes; sequences containing this entry in photosynthetic organisms are possible false positives.
The clan contains the following 5 members:
Dehalogenase MMACHC MMADHC Nitroreductase TM1586_NiRdaseAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (74) |
Full (29252) |
Representative proteomes | UniProt (138070) |
NCBI (181770) |
Meta (3542) |
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| RP15 (3361) |
RP35 (13576) |
RP55 (28872) |
RP75 (51592) |
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| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
| Seed (74) |
Full (29252) |
Representative proteomes | UniProt (138070) |
NCBI (181770) |
Meta (3542) |
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|---|---|---|---|---|---|---|---|---|---|
| RP15 (3361) |
RP35 (13576) |
RP55 (28872) |
RP75 (51592) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_481 (release 3.0) |
| Previous IDs: | none |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Bateman A 
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| Number in seed: | 74 |
| Number in full: | 29252 |
| Average length of the domain: | 148.00 aa |
| Average identity of full alignment: | 17 % |
| Average coverage of the sequence by the domain: | 65.51 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 168 | ||||||||||||
| Family (HMM) version: | 25 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
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Eukaryota
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Interactions
There is 1 interaction for this family. More...
NitroreductaseStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Nitroreductase domain has been found. There are 327 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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