PDBsum entry 4tw5

Isomerase

PDB id: 4tw5

Contents

Protein chains

264 a.a.

Waters ×240

PDB id:

4tw5

Name:

Isomerase

Title:

Structure of the first two thioredoxin domains of saccharomyces cerevisiae eps1p

Structure:

Eps1p. Chain: a, b, c, d. Fragment: unp residues 28-295. Engineered: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 574961. Strain: jay291. Gene: eps1, c1q_00313. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.37Å R-factor: 0.215 R-free: 0.272

Authors:

D.Fass,S.Biran

Key ref:

S.Biran et al. (2014). The Eps1p protein disulfide isomerase conserves classic thioredoxin superfamily amino acid motifs but not their functional geometries. Plos One, 9, e113431. PubMed id: 25437863 DOI: 10.1371/journal.pone.0113431

Date:

30-Jun-14 Release date: 17-Dec-14

Protein chains

C7GJH6  (C7GJH6_YEAS2) -  Eps1p from Saccharomyces cerevisiae (strain JAY291)

Seq: 701 a.a.

Struc: 264 a.a.

Enzyme reactions

• Enzyme class: E.C.5.4.3.1 - Deleted entry.

DOI no: 10.1371/journal.pone.0113431

Plos One 9:e113431 (2014)

PubMed id: 25437863

The Eps1p protein disulfide isomerase conserves classic thioredoxin superfamily amino acid motifs but not their functional geometries.

S.Biran, Y.Gat, D.Fass.

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.