PDBsum entry 3cy6

Unknown function

PDB id: 3cy6

Contents

Protein chain

186 a.a. *

Waters ×193

* Residue conservation analysis

PDB id:

3cy6

Name:

Unknown function

Title:

Crystal structure of e18q dj-1

Structure:

Protein dj-1. Chain: a. Synonym: oncogene dj1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: park7. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.35Å R-factor: 0.155 R-free: 0.168

Authors:

A.C.Witt,M.Lakshminarasimhan,B.C.Remington,S.Hasim,E.Pozharski, M.A.Wilson

Key ref:

A.C.Witt et al. (2008). Cysteine pKa depression by a protonated glutamic acid in human DJ-1. Biochemistry, 47, 7430-7440. PubMed id: 18570440

Date:

25-Apr-08 Release date: 01-Jul-08

Protein chain

Q99497  (PARK7_HUMAN) -  Parkinson disease protein 7 from Homo sapiens

Seq: 189 a.a.

Struc: 186 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.5.1.124 - protein deglycase.
• Reaction:
  1. N(omega)-(1-hydroxy-2-oxopropyl)-L-arginyl-[protein] + H2O = lactate + L-arginyl-[protein] + H⁺
  2. N₆-(1-hydroxy-2-oxopropyl)-L-lysyl-[protein] + H2O = lactate + L-lysyl-[protein] + H⁺
  3. S-(1-hydroxy-2-oxopropyl)-L-cysteinyl-[protein] + H2O = lactate + L-cysteinyl-[protein] + H⁺

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

reference

Biochemistry 47:7430-7440 (2008)

PubMed id: 18570440

Cysteine pKa depression by a protonated glutamic acid in human DJ-1.

A.C.Witt, M.Lakshminarasimhan, B.C.Remington, S.Hasim, E.Pozharski, M.A.Wilson.

ABSTRACT

Human DJ-1, a disease-associated protein that protects cells from oxidative stress, contains an oxidation-sensitive cysteine (C106) that is essential for its cytoprotective activity. The origin of C106 reactivity is obscure, due in part to the absence of an experimentally determined p K a value for this residue. We have used atomic-resolution X-ray crystallography and UV spectroscopy to show that C106 has a depressed p K a of 5.4 +/- 0.1 and that the C106 thiolate accepts a hydrogen bond from a protonated glutamic acid side chain (E18). X-ray crystal structures and cysteine p K a analysis of several site-directed substitutions at residue 18 demonstrate that the protonated carboxylic acid side chain of E18 is required for the maximal stabilization of the C106 thiolate. A nearby arginine residue (R48) participates in a guanidinium stacking interaction with R28 from the other monomer in the DJ-1 dimer and elevates the p K a of C106 by binding an anion that electrostatically suppresses thiol ionization. Our results show that the ionizable residues (E18, R48, and R28) surrounding C106 affect its p K a in a way that is contrary to expectations based on the typical ionization behavior of glutamic acid and arginine. Lastly, a search of the Protein Data Bank (PDB) produces several candidate hydrogen-bonded aspartic/glutamic acid-cysteine interactions, which we propose are particularly common in the DJ-1 superfamily.