Summary: DSBA-like thioredoxin domain
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Crystal structure of E. coli DsbA.
DsbA is a bacterial thiol disulfide oxidoreductases (TDOR). DsbA is a key component of the Dsb (disulfide bond) family of enzymes. DsbA catalyzes intrachain disulfide bond formation as peptides emerge into the cell's periplasm.
Structurally, DsbA contains a thioredoxin domain with an inserted helical domain of unknown function. Like other thioredoxin-based enzymes, DsbA's catalytic site is a CXXC motif (CPHC in E. coli DsbA). The pair of cysteines may be oxidized (forming an internal disulfide) or reduced (as free thiols), and thus allows for oxidoreductase activity by serving as an electron pair donor or acceptor, depending on oxidation state. This reaction generally proceeds through a mixed-disulfide intermediate, in which a cysteine from the enzyme forms a bond to a cysteine on the substrate. DsbA is responsible for introducing disulfide bonds into nascent proteins. In equivalent terms, it catalyzes the oxidation of a pair of cysteine residues on the substrate protein. Most of the substrates for DsbA are eventually secreted, and include important toxins, virulence factors, adhesion machinery, and motility structures DsbA is localized in the periplasm, and is more common in Gram-negative bacteria than in Gram-positive bacteria. Within the thioredoxin family, DsbA is the most strongly oxidizing. Using glutathione oxidation as a metric, DsbA is ten times more oxidizing than protein disulfide-isomerase (the eukaryotic equivalent of DsbA). The extremely oxidizing nature of DsbA is due to an increase in stability upon reduction of DsbA, thereby imparting a decrease in energy of the enzyme when it oxidizes substrate. This feature is incredibly rare among proteins, as nearly all proteins are stabilized by the formation of disulfide bonds. DsbA's highly oxidizing nature is a result of hydrogen bond, electrostatic and helix-dipole interactions that favour the thiolate over the disulfide at the active site.
After donating its disulfide bond, DsbA is regenerated by the membrane-bound protein DsbB.
- Guddat, LW. "RCSB Protein Data Bank - RCSB PDB - 1A2M Structure Summary". Retrieved 11 July 2012.
- Kadokura, H.; Beckwith, J. (Sep 2009). "Detecting folding intermediates of a protein as it passes through the bacterial translocation channel.". Cell 138 (6): 1164–73. doi:10.1016/j.cell.2009.07.030. PMID 19766568.
- Guddat, LW; Bardwell, JC; Martin, JL (Jun 15, 1998). "Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization.". Structure (London, England : 1993) 6 (6): 757–67. doi:10.1016/S0969-2126(98)00077-X. PMID 9655827.
- Heras, Begoña; Shouldice, Stephen R.; Totsika, Makrina; Scanlon, Martin J.; Schembri, Mark A.; Martin, Jennifer L. (9 February 2009). "DSB proteins and bacterial pathogenicity". Nature Reviews Microbiology 7 (3): 215–225. doi:10.1038/nrmicro2087.
- Zapun, A; Bardwell, JC; Creighton, TE (May 18, 1993). "The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo.". Biochemistry 32 (19): 5083–92. doi:10.1021/bi00070a016. PMID 8494885.
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.
DSBA-like thioredoxin domain Provide feedback
This family contains a diverse set of proteins with a thioredoxin-like structure PF00085. This family also includes 2-hydroxychromene-2-carboxylate (HCCA) isomerase enzymes catalyse one step in prokaryotic polyaromatic hydrocarbon (PAH) catabolic pathways [2,3,4]. This family also contains members with functions other than HCCA isomerisation, such as Kappa family GSTs (e.g. P24473), whose similarity to HCCA isomerases was not previously recognised. The sequence O07298 has been annotated as a dioxygenase but is almost certainly an HCCA isomerase enzyme. Similarly, the sequence Q9ZI67 has been annotated as a dehydrogenase, but is most probably also an HCCA isomerase enzyme. In addition, the Rhizobium leguminosarum Q52782 protein has been annotated as a putative glycerol-3-phosphate transfer protein, but is also most likely to be an HCCA isomerase enzyme (see ).
Denome SA, Stanley DC, Olson ES, Young KD; , J Bacteriol 1993;175:6890-6901.: Metabolism of dibenzothiophene and naphthalene in Pseudomonas strains: complete DNA sequence of an upper naphthalene catabolic pathway. PUBMED:8226631 EPMC:8226631
Eaton RW; , J Bacteriol 1994;176:7757-7762.: Organization and evolution of naphthalene catabolic pathways: sequence of the DNA encoding 2-hydroxychromene-2-carboxylate isomerase and trans-o-hydroxybenzylidenepyruvate hydratase-aldolase from the NAH7 plasmid. PUBMED:8002605 EPMC:8002605
Laurie AD, Lloyd-Jones G; , J Bacteriol 1999;181:531-540.: The phn genes of Burkholderia sp. strain RP007 constitute a divergent gene cluster for polycyclic aromatic hydrocarbon catabolism. PUBMED:9882667 EPMC:9882667
Brito B, Palacios JM, Ruiz-Argueso T, Imperial J; , Biochim Biophys Acta 1996;1308:7-11.: Identification of a gene for a chemoreceptor of the methyl-accepting type in the symbiotic plasmid of Rhizobium leguminosarum bv. viciae UPM791. PUBMED:8765742 EPMC:8765742
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001853DSBA is a sub-family of the Thioredoxin family [PUBMED:9149147]. The efficient and correct folding of bacterial disulphide bonded proteins in vivo is dependent upon a class of periplasmic oxidoreductase proteins called DsbA, after the Escherichia coli enzyme. The bacterial protein-folding factor DsbA is the most oxidizing of the thioredoxin family. DsbA catalyses disulphide-bond formation during the folding of secreted proteins. The extremely oxidizing nature of DsbA has been proposed to result from either domain motion or stabilising active-site interactions in the reduced form. DsbA's highly oxidizing nature is a result of hydrogen bond, electrostatic and helix-dipole interactions that favour the thiolate over the disulphide at the active site [PUBMED:9655827]. In the pathogenic bacterium Vibrio cholerae, the DsbA homologue (TcpG) is responsible for the folding, maturation and secretion of virulence factors.
While the overall architecture of TcpG and DsbA is similar and the surface features are retained in TcpG, there are significant differences. For example, the kinked active site helix results from a three-residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more similar to thioredoxin in this respect). Furthermore, the proposed peptide binding groove of TcpG is substantially shortened compared with that of DsbA due to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow and the acidic patch is much less extensive than that of E. coli DsbA [PUBMED:9149147].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein disulfide oxidoreductase activity (GO:0015035)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains families related to the thioredoxin family. Thioredoxins are small enzymes that are involved in redox reactions via the reversible oxidation of an active centre disulfide bond. The thioredoxin fold consists of a 3 layer alpha/beta/alpha sandwich and a central beta sheet.
The clan contains the following 57 members:2Fe-2S_thioredx AhpC-TSA AhpC-TSA_2 Aminopep ArsC ArsD Calsequestrin DIM1 DSBA DUF1223 DUF1462 DUF1525 DUF1687 DUF2703 DUF2847 DUF4174 DUF836 DUF899 DUF953 ERp29_N GILT Glutaredoxin GSHPx GST_N GST_N_2 GST_N_3 GST_N_4 HyaE KaiB L51_S25_CI-B8 Metallopep MRP-S23 MRP-S25 OST3_OST6 Peptidase_M76 Phosducin Rdx Redoxin SCO1-SenC SelP_N Sep15_SelM SH3BGR T4_deiodinase Thioredox_DsbH Thioredoxin Thioredoxin_2 Thioredoxin_3 Thioredoxin_4 Thioredoxin_5 Thioredoxin_6 Thioredoxin_7 Thioredoxin_8 Thioredoxin_9 Tom37 TraF YtfJ_HI0045 Zincin_1
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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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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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.
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Curation and family details
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|Seed source:||Bateman A & Pfam-B_2082 (release 6.4) & Pfam-B_5982 (Release 7.5)|
|Author:||Bateman A, Mifsud W|
|Number in seed:||30|
|Number in full:||3893|
|Average length of the domain:||180.00 aa|
|Average identity of full alignment:||18 %|
|Average coverage of the sequence by the domain:||79.79 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
|Download:||download the raw HMM for this family|
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This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 DSBA domain has been found. There are 120 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 seqence.
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