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505  structures 5852  species 0  interactions 15736  sequences 103  architectures

Family: DSBA (PF01323)

Summary: DSBA-like thioredoxin domain

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This is the Wikipedia entry entitled "DsbA". More...

DsbA Edit Wikipedia article

Ecoli DsbA 1A2M.png
Crystal structure of E. coli DsbA.[1]
NCBI gene948353
DSBA oxidoreductase

DsbA is a bacterial thiol disulfide oxidoreductase (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.[2]

Structurally, DsbA contains a thioredoxin domain with an inserted helical domain of unknown function.[3] 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[4] 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 member. 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.[5] 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.

See also


  1. ^ Guddat, LW (1998). "RCSB Protein Data Bank - RCSB PDB - 1A2M Structure Summary". Structure. 6: 757–767. doi:10.2210/pdb1a2m/pdb. Retrieved 11 July 2012.
  2. ^ Kadokura H, Beckwith J (September 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. PMC 2750780. PMID 19766568.
  3. ^ Guddat LW, Bardwell JC, Martin JL (June 1998). "Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization". Structure. 6 (6): 757–67. doi:10.1016/S0969-2126(98)00077-X. PMID 9655827.
  4. ^ Heras B, Shouldice SR, Totsika M, Scanlon MJ, Schembri MA, Martin JL (March 2009). "DSB proteins and bacterial pathogenicity". Nature Reviews. Microbiology. 7 (3): 215–25. doi:10.1038/nrmicro2087. PMID 19198617. S2CID 34433130.
  5. ^ Zapun A, Bardwell JC, Creighton TE (May 1993). "The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo". Biochemistry. 32 (19): 5083–92. CiteSeerX doi:10.1021/bi00070a016. PMID 8494885.
This article incorporates text from the public domain Pfam and InterPro: IPR001853

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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 [5]).

Literature references

  1. Hu SH, Peek JA, Rattigan E, Taylor RK, Martin JL; , J Mol Biol 1997;268:137-146.: Structure of TcpG, the DsbA protein folding catalyst from Vibrio cholerae. PUBMED:9149147 EPMC:9149147

  2. 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

  3. 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

  4. 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

  5. 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

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001853

DSBA 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 ].

Gene Ontology

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Domain organisation

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Seed source: Bateman A & Pfam-B_2082 (release 6.4) & Pfam-B_5982 (Release 7.5)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Mifsud W
Number in seed: 30
Number in full: 15736
Average length of the domain: 181.70 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 81.25 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.6 25.6
Trusted cut-off 25.6 25.6
Noise cut-off 25.5 25.5
Model length: 193
Family (HMM) version: 23
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 505 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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