PDBsum entry 4qyt

Unknown function

PDB id: 4qyt

Contents

Protein chains

190 a.a.

Ligands

EDO ×8

Metals

_MG ×5

Waters ×903

PDB id:

4qyt

Name:

Unknown function

Title:

Schizosaccharomyces pombe dj-1

Structure:

Uncharacterized protein c22e12.03c. Chain: a, b, c, d. Synonym: dj-1. Engineered: yes

Source:

Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Gene: spac22e12.03c. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.05Å R-factor: 0.111 R-free: 0.132

Authors:

M.A.Wilson

Key ref:

P.Madzelan et al. (2012). Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values in fission yeast DJ-1. Febs J, 279, 4111-4120. PubMed id: 22971103

Date:

25-Jul-14 Release date: 06-Aug-14

Supersedes:

4gdh

Protein chains

Q10356  (DJ1_SCHPO) -  Glutathione-independent glyoxalase DJ-1 from Schizosaccharomyces pombe (strain 972 / ATCC 24843)

Seq: 191 a.a.

Struc: 190 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.2.1.130 - D-lactate dehydratase.
• Reaction: methylglyoxal + H2O = (R)-lactate + H⁺

methylglyoxal + H2O (Bound ligand (Het Group name = EDO) matches with 80.00% similarity) = (R)-lactate + H(+)

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

Added reference

Febs J 279:4111-4120 (2012)

PubMed id: 22971103

Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values in fission yeast DJ-1.

P.Madzelan, T.Labunska, M.A.Wilson.

ABSTRACT

Cysteine residues with depressed pK(a) values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N-termini of α-helices. Using a combination of X-ray crystallography, site-directed mutagenesis and spectroscopic methods, we show that the reactive cysteine residue (Cys111) in Schizosaccharomyces pombe DJ-1 experiences a 0.6 unit depression of its thiol pK(a) as a consequence of a hydrogen bond donated by a threonine side chain (Thr114) to a nearby peptide carbonyl oxygen at the N-terminus of an α-helix. This extended hydrogen bonded interaction is consistent with a sum of dipoles model whereby the distal hydrogen bond polarizes and strengthens the direct hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate). Therefore, our results suggest that the local dipolar enhancement of hydrogen bonds can appreciably stabilize cysteine thiolate formation. However, the substitution of a valine residue with a proline at the i + 3 position has only a minor effect (0.3 units) on the pK(a) of Cys111. As proline has a reduced peptide dipole moment, this small effect suggests that a more extended helix macrodipolar effect does not play a major role in this system. DATABASE: Structural models and diffraction data are available in the Protein Data Bank under the accession number(s) 4GDH (wild-type SpDJ-1), 4GE0 (T114P SpDJ-1) and 4GE3 (T114V SpDJ-1) STRUCTURED DIGITAL ABSTRACT: SpDJ-1 and SpDJ-1 bind by x-ray crystallography (View interaction).