Warning: mysql_result() [function.mysql-result]: Unable to jump to row 0 on MySQL result index 5 in /net/isilon4/research/thornton/www/databases/html/CSA/SearchResults.php on line 84
Catalytic Site Atlas Search Results
View the latest EBI news stories and important announcements...

Search The CSA
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 2hi7

SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 1.8.4.-
CSA Homologues of 2hi7
CSA Entries With UniProtID
CSA Entries With EC Number 1.8.4.-
PDBe Entry 2hi7
PDBSum Entry 2hi7
MACiE Entry 2hi7

Literature Report

IntroductionDsbB isolated from Escherichia coli is able to create disulfide bonds de novo. It forms a complex with DsbA and overall there is a net formation of a disulfide bridge in DsbA and a quinone cofactor is reduced in DsbB. The quinone can either be ubiquinone (under aerobic conditions) or menaquinone (under anaerobic conditions). DsbA is a periplasmic dithiol oxidase and it is the primary disulfide bond donor in the periplasm.
The disulfide bond to be produced in DsbA is between Cys30 and Cys33. Two disulfide bonds exist in DsbB in the resting state, Cys41-Cys44 and Cys104-Cys130; they are involved in the catalytic pathway.
MechansimThere is nucleophilic attack on the DsbB Cys104-Cys130 disulfide bridge by the DsbA Cys30 thiolate, leading to a Cys104-Cys30 intermolecular disulfide bond and a Cys130 thiolate. There is nucleophilic attack by the DsbA Cys33 thiolate on the intermolecular disulfide bond leading to a Cys30-Cys33 intramolecular disulfide bond and a Cys104 thiolate. The hemi-oxidised DsbB then rearranges so that the Cys41-Cys44 disulfide bond is reduced and Cys104 and Cys130 are oxidised to form a bond. The Cys44 thiolate forms a charge transfer complex with the quinone, stabilised by Arg48, and then forms an adduct through the C2 of the quinone. The negative charge is delocalised around the O2 atom and is also stabilised by Arg48. The Cys41 thiolate then acts as a nucleophile and attacks Cys44, breaking the S-C2 bond and creating a disulfide bridge and a reduced quinone molecule.
The above refers to the rapid pathway, which predominates. There is a minor pathway called the slow pathway. The two diverge after the formation of the intermolecular disulfide bond. In the slow pathway there is nucleophilic attack on the Cys41-Cys44 disulfide bond by the Cys130 thiolate, leading to a Cys41-Cys130 disulfide bond and a Cys44 thiolate. The exact mechanism by which the final disulfide bonds are generated and the quinone is reduced is unknown.

Catalytic Sites for 2hi7

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysB4444macie:sideChainThe Cys41-Cys44 disulfide bond is reduced in the hemi-oxidised DsbB. The Cys44 thiolate forms a charge transfer complex with the quinone and then an adduct. The sulfur acts as the electrophile in the nucleophilic substitution by Cys41, thus reforming the disulfide bond.
ArgB4848macie:sideChainArg48 stabilises the charge transfer complex between the Cys44 thiolate and the quinone. It also stabilises the adduct formed between the two.
CysB104104macie:sideChainThe Cys104-Cys130 bond is cleaved by nucleophilic attack by the Cys30 thiolate, forming a Cys104-Cys30 bond. This bond is then cleaved after nucleophilic attack by the Cys33 thiolate, leaving Cys104 as a thiolate. The rearrangement of the hemi-oxidised DsbB allows the Cys104-Cys130 bond to reform when the Cys41-Cys44 bond is reduced.
CysB4141macie:sideChainThe Cys41-Cys44 disulfide bond is reduced in the hemi-oxidised DsbB. The Cys41 thiolate attacks the Cys44-quinone adduct to reform the Cys41-Cys44 disulfide bond.

Literature References

Inaba K
Crystal structure of the DsbB-DsbA complex reveals a mechanism of disulfide bond generation.
Cell 2006 127 789-801
PubMed: 17110337