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Tbk2109 (talk | contribs)
9 edits
Fixed wording in the first sentence and replaced all the wrong uniprot and entrezgene info for motB (a completely different protein)
Tbk2109 (talk | contribs)
9 edits
Replaced Salmonella structure with E. coli structure, removed robotic analysis of structure (it has no meaning), changed category to "enzymes", significant additions and replacements
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{{Infobox protein
{{Infobox protein
| Name = DsbA
| Name = DsbA
| image =3L9S.pdb.jpg
| image =Ecoli DsbA 1A2M.png
| width =
| width =
| caption =Crystal structure of DsbA.<ref name="urlRCSB Protein Data Bank - Structure Summary for 3L9S - Crystal structure of DsbA ">{{PDB|3L9S}}; {{cite web | url = http://www.pdb.org/pdb/explore/remediatedSequence.do?structureId=3L9S| title = RCSB Protein Data Bank - Structure Summary for 3L9S - Crystal structure of | author = | authorlink = | coauthors = | date = | format = | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
| caption =Crystal structure of E. coli DsbA. <ref name="1A2M at RCSB PDB">{{cite web|last=Guddat|first=LW|title=RCSB Protein Data Bank - RCSB PDB - 1A2M Structure Summary|url=http://www.rcsb.org/pdb/explore.do?structureId=1A2M|accessdate=11 July 2012}}</ref>
| Symbol = DsbA
| Symbol = DsbA
| AltSymbols =
| AltSymbols =
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| HGNCid =
| HGNCid =
| OMIM =
| OMIM =
| PDB =
| PDB = 1A2M
| RefSeq =
| RefSeq =
| UniProt = P0AEG4
| UniProt = P0AEG4
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{{Pfam box |Symbol = DSBA |Name = DSBA oxidoreductase |Pfam = PF01323 |InterPro = IPR001853 |PROSITE = |PDB = {{PDB|1a2l}} {{PDB|1a2m}} {{PDB|1ac1}} {{PDB|1acv}} {{PDB|1bed}} {{PDB|1bq7}} {{PDB|1dsb}} {{PDB|1fvj}} {{PDB|1fvk}} {{PDB|1r4w}} }}
{{Pfam box |Symbol = DSBA |Name = DSBA oxidoreductase |Pfam = PF01323 |InterPro = IPR001853 |PROSITE = |PDB = {{PDB|1a2l}} {{PDB|1a2m}} {{PDB|1ac1}} {{PDB|1acv}} {{PDB|1bed}} {{PDB|1bq7}} {{PDB|1dsb}} {{PDB|1fvj}} {{PDB|1fvk}} {{PDB|1r4w}} }}


'''DsbA''' is a disulfide oxidoreductase containing a [[Thioredoxin fold]] with an inserted helical domain of unknown function.<ref name="1A2M paper">{{cite journal|last=Guddat|first=LW|coauthors=Bardwell, JC; Martin, JL|title=Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization.|journal=Structure (London, England : 1993)|date=1998 Jun 15|volume=6|issue=6|pages=757-67|doi=10.1016/S0969-2126(98)00077-X|pmid=9655827|accessdate=11 July 2012}}</ref> Like other thioredoxin-based enzymes, DsbA's catalytic motif is a CXXC (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<ref name="DSB proteins and bacterial pathogenicity">{{cite journal|last=Heras|first=Begoña|coauthors=Shouldice, Stephen R.; Totsika, Makrina; Scanlon, Martin J.; Schembri, Mark A.; Martin, Jennifer L.|title=DSB proteins and bacterial pathogenicity|journal=Nature Reviews Microbiology|date=9 February 2009|volume=7|issue=3|pages=215–225|doi=doi:10.1038/nrmicro2087|accessdate=11 July 2012}}</ref> 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.<ref name="The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo.">{{cite journal|last=Zapun|first=A|coauthors=Bardwell, JC; Creighton, TE|title=The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo.|journal=Biochemistry|date=1993 May 18|volume=32|issue=19|pages=5083-92|doi=dx.doi.org/10.1021/bi00070a016|pmid=8494885|accessdate=11 July 2012}}</ref> 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.
'''DsbA''' is an oxidoreductase with a [[Thioredoxin fold]].<ref name="PUB00003378">{{cite journal |author=Hu SH, Peek JA, Rattigan E, Taylor RK, Martin JL |title=Structure of TcpG, the DsbA protein folding catalyst
<gallery>
File:
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</gallery>
from Vibrio cholerae |journal=J. Mol. Biol. |volume=268 |issue=1 |pages=137–146 |year=1997 |pmid=9149147 |doi=10.1006/jmbi.1997.0940}}</ref> The efficient and correct folding of bacterial disulfide 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 catalyzes disulfide-bond formation during the folding of secreted proteins. The extremely oxidizing nature of DsbA has been proposed to result from either domain motion or stabilizing 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 disulfide at the active site.<ref name="PUB00006416">{{cite journal |author=Bardwell JC, Martin JL, Guddat LW |title=Crystal structures of reduced and oxidized DsbA: investigation of domain motion and thiolate stabilization |journal=Structure |volume=6 |issue=6 |pages=757–767 |year=1998 |pmid=9655827}}</ref> In the pathogenic bacterium ''[[Vibrio cholerae]]'', the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion of virulence factors.

Sequence/ Structure Details:.<ref name="urlRCSB Protein Data Bank - Structure Summary for 3L9S - Crystal structure of DsbA "/> The structure 3L9S has in total 1 chains. Out of these 1 are sequence-unique. The structure of the crystal is composed of 50% helical (9 helices; 97 residues) and 10% beta sheet (6 strands; 21 residues).<ref>{{cite book|last=Horwich|first=Arthur|title=Advances in protein chemistry|year=2002|publisher=Academic Press|pages=284–287|url=http://books.google.com/books?id=3ipKFrFpxD4C&lpg=PA285&ots=DzSLZDei_o&dq=motility%20protein%20dsba&pg=PR4#v=onepage&q=motility%20protein%20dsba&f=false}}</ref> The crystal structure of DsbA contains a thioredoxin like fold which includes a central β-strand in the central β-sheet and the insertion of a 65 residue helical domain. These insertions are common within the thioredoxin family.


==References==
==References==
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{{DEFAULTSORT:Dsba}}
{{DEFAULTSORT:Dsba}}
[[Category:Protein folding]]
[[Category:Enzymes]]

Revision as of 19:53, 11 July 2012

DsbA
Crystal structure of E. coli DsbA. [1]
Identifiers
SymbolDsbA
NCBI gene948353
PDB1A2M
UniProtP0AEG4
Search for
StructuresSwiss-model
DomainsInterPro
DSBA oxidoreductase
Identifiers
SymbolDSBA
PfamPF01323
InterProIPR001853
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDBPDB: 1a2l​ PDB: 1a2m​ PDB: 1ac1​ PDB: 1acv​ PDB: 1bed​ PDB: 1bq7​ PDB: 1dsb​ PDB: 1fvj​ PDB: 1fvk​ PDB: 1r4w​

DsbA is a disulfide oxidoreductase containing a Thioredoxin fold with an inserted helical domain of unknown function.[2] Like other thioredoxin-based enzymes, DsbA's catalytic motif is a CXXC (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[3] 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.[4] 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.

References

  1. ^ Guddat, LW. "RCSB Protein Data Bank - RCSB PDB - 1A2M Structure Summary". Retrieved 11 July 2012.
  2. ^ Guddat, LW (1998 Jun 15). "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. {{cite journal}}: |access-date= requires |url= (help); Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  3. ^ Heras, Begoña (9 February 2009). "DSB proteins and bacterial pathogenicity". Nature Reviews Microbiology. 7 (3): 215–225. doi:doi:10.1038/nrmicro2087. {{cite journal}}: |access-date= requires |url= (help); Check |doi= value (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  4. ^ Zapun, A (1993 May 18). "The reactive and destabilizing disulfide bond of DsbA, a protein required for protein disulfide bond formation in vivo". Biochemistry. 32 (19): 5083–92. doi:dx.doi.org/10.1021/bi00070a016. PMID 8494885. {{cite journal}}: |access-date= requires |url= (help); Check |doi= value (help); Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
This article incorporates text from the public domain Pfam and InterPro: IPR001853
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