title: Trimeric structure of PRL-1 phosphatase reveals an active enzyme conformation and regulation mechanisms.
abstract: The PRL phosphatases, which constitute a subfamily of the protein tyrosine phosphatases (PTPs), are implicated in oncogenic and metastatic processes. Here, we report the crystal structure of human PRL-1 determined at 2.7A resolution. The crystal structure reveals the shallow active-site pocket with highly hydrophobic character. A structural comparison with the previously determined NMR structure of PRL-3 exhibits significant differences in the active-site region. In the PRL-1 structure, a sulfate ion is bound to the active-site, providing stabilizing interactions to maintain the canonically found active conformation of PTPs, whereas the NMR structure exhibits an open conformation of the active-site. We also found that PRL-1 forms a trimer in the crystal and the trimer exists in the membrane fraction of cells, suggesting the possible biological regulation of PRL-1 activity by oligomerization. The detailed structural information on the active enzyme conformation and regulation of PRL-1 provides the structural basis for the development of potential inhibitors of PRL enzymes.
authors.affiliation: Center for Cellular Switch Protein Structure, Korea Research Institute of Bioscience and Biotechnology, 52 Euh-eun-dong, Yuseong-gu, Daejeon 305-806, South Korea.
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Son
authors.forename: Mi Rim
authors.initials: MR
authors.lastname: Park
authors.forename: Sang Myoun
authors.initials: SM
authors.lastname: Lim
authors.forename: Tae-Sung
authors.initials: TS
authors.lastname: Yoon
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins; D018360:Crystallography, X-Ray; D019281:Dimerization; D004583:Electrons; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry*; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions; D013379:Substrate Specificity
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010455:Peptides; C490198:PTP4A1 protein, human; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases