 |
PDBsum entry 4tw5
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
The eps1p protein disulfide isomerase conserves classic thioredoxin superfamily amino acid motifs but not their functional geometries.
|
|
|
Authors
|
|
S.Biran,
Y.Gat,
D.Fass.
|
|
|
Ref.
|
|
Plos One, 2014,
9,
e113431.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The widespread thioredoxin superfamily enzymes typically share the following
features: a characteristic α-β fold, the presence of a Cys-X-X-Cys (or
Cys-X-X-Ser) redox-active motif, and a proline in the cis configuration abutting
the redox-active site in the tertiary structure. The Cys-X-X-Cys motif is at the
solvent-exposed amino terminus of an α-helix, allowing the first cysteine to
engage in nucleophilic attack on substrates, or substrates to attack the
Cys-X-X-Cys disulfide, depending on whether the enzyme functions to reduce,
isomerize, or oxidize its targets. We report here the X-ray crystal structure of
an enzyme that breaks many of our assumptions regarding the sequence-structure
relationship of thioredoxin superfamily proteins. The yeast Protein Disulfide
Isomerase family member Eps1p has Cys-X-X-Cys motifs and proline residues at the
appropriate primary structural positions in its first two predicted
thioredoxin-fold domains. However, crystal structures show that the Cys-X-X-Cys
of the second domain is buried and that the adjacent proline is in the trans,
rather than the cis isomer. In these configurations, neither the
"active-site" disulfide nor the backbone carbonyl preceding the
proline is available to interact with substrate. The Eps1p structures thus
expand the documented diversity of the PDI oxidoreductase family and demonstrate
that conserved sequence motifs in common folds do not guarantee structural or
functional conservation.
|
|
|
|
|
|
|
