title: The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease.
abstract: DJ-1 is a multifunctional protein that plays essential roles in tissues with higher order biological functions such as the testis and brain. DJ-1 is related to male fertility, and its level in sperm decreases in response to exposure to sperm toxicants. DJ-1 has also been identified as a hydroperoxide-responsive protein. Recently, a mutation of DJ-1 was found to be responsible for familial Parkinson's disease. Here, we present the crystal structure of DJ-1 refined to 1.95-A resolution. DJ-1 forms a dimer in the crystal, and the monomer takes a flavodoxin-like Rossmann-fold. DJ-1 is structurally most similar to the monomer subunit of protease I, the intracellular cysteine protease from Pyrococcus horikoshii, and belongs to the Class I glutamine amidotransferase-like superfamily. However, DJ-1 contains an additional alpha-helix at the C-terminal region, which blocks the putative catalytic site of DJ-1 and appears to regulate the enzymatic activity. DJ-1 may induce conformational changes to acquire catalytic activity in response to oxidative stress.
authors.affiliation: Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, N-12, W-6, Kita-ku, Sapporo, 060-0812, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Honbou
authors.forename: Nobuo N
authors.initials: NN
authors.lastname: Suzuki
authors.forename: Masataka
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Taira
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Inagaki
mesh_terms: D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D005298:Fertility / Q000502:physiology; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D015513:Oncogene Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1