PDBsum entry 4l0w

Oxidoreductase

PDB id: 4l0w

Contents

Protein chain

173 a.a.

Ligands

ACT

SO4

Waters ×74

PDB id:

4l0w

Name:

Oxidoreductase

Title:

Plasmodium yoelii prx1a modified at the n-terminus forms an artifactual octamer

Structure:

Thioredoxin peroxidase 1. Chain: a. Fragment: residues 8-125. Engineered: yes

Source:

Plasmodium yoelii yoelii. Organism_taxid: 73239. Strain: 17xnl. Gene: py00414. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.29Å R-factor: 0.198 R-free: 0.246

Authors:

M.C.Gretes,P.A.Karplus

Key ref:

M.C.Gretes and P.A.Karplus (2013). Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native "ball-and-socket" interacting residues by an affinity tag. Protein Sci, 22, 1445-1452. PubMed id: 23934758

Date:

01-Jun-13 Release date: 09-Nov-16

Protein chain

Q7RSE5  (Q7RSE5_PLAYO) -  thioredoxin-dependent peroxiredoxin from Plasmodium yoelii yoelii

Seq: 195 a.a.

Struc: 173 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.11.1.24 - thioredoxin-dependent peroxiredoxin.
• Reaction: a hydroperoxide + [thioredoxin]-dithiol = an alcohol + [thioredoxin]- disulfide + H2O

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Protein Sci 22:1445-1452 (2013)

PubMed id: 23934758

Observed octameric assembly of a Plasmodium yoelii peroxiredoxin can be explained by the replacement of native "ball-and-socket" interacting residues by an affinity tag.

M.C.Gretes, P.A.Karplus.

ABSTRACT

Peroxiredoxins (Prxs) are ubiquitous and efficient antioxidant enzymes crucial for redox homeostasis in most organisms, and are of special importance for disease-causing parasites that must protect themselves against the oxidative weapons of the human immune system. Here, we describe reanalyses of crystal structures of two Prxs from malaria parasites. In addition to producing improved structures, we provide normalizing explanations for features that had been noted as unusual in the original report of these structures (Qiu et al., BMC Struct Biol 2012;12:2). Most importantly, we provide evidence that the unusual octameric assembly seen for Plasmodium yoelii Prx1a is not physiologically relevant, but arises because the structure is not of authentic P. yoelii Prx1a, but a variant we designate PyPrx1a(N*) that has seven native N-terminal residues replaced by an affinity tag. This N-terminal modification disrupts a previously unrecognized, hydrophobic "ball-and-socket" interaction conserved at the B-type dimer interface of Prx1 subfamily enzymes, and is accommodated by a fascinating two-residue "β-slip" type register shift in the β-strand association at a dimer interface. The resulting change in the geometry of the dimer provides a simple explanation for octamer formation. This study illustrates how substantive impacts can occur in protein variants in which native residues have been altered.