title: Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity.
abstract: Myotubularin-related protein 1 (MTMR1) is a phosphatase that belongs to the tyrosine/dual-specificity phosphatase superfamily. MTMR1 has been shown to use phosphatidylinositol 3-monophosphate (PI(3)P) and/or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) as substrates. Here, we determined the crystal structure of human MTMR1. The refined model consists of the Pleckstrin homology (PH)-GRAM and phosphatase (PTP) domains. The overall structure was highly similar to the previously reported MTMR2 structure. Interestingly, two phosphate molecules were coordinated by strictly conserved residues located in the C(X)5R motif of the active site. Additionally, our biochemical studies confirmed the substrate specificity of MTMR1 for PI(3)P and PI(3,5)P2 over other phosphatidylinositol phosphates. Our structural and enzymatic analyses provide insight into the catalytic mechanism and biochemical properties of MTMR1.
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Seoung Min
authors.initials: SM
authors.lastname: Bong
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Kka-bi
authors.initials: KB
authors.lastname: Son
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Yang
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Jea-Won
authors.initials: JW
authors.lastname: Cho
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Hackyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Chemistry, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
authors.forename: Byung Il
authors.initials: BI
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017434:Protein Structure, Tertiary; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D018129:Phosphatidylinositol Phosphates; D011994:Recombinant Proteins; C106336:phosphatidylinositol 3,5-diphosphate; C055525:phosphatidylinositol 3-phosphate; C116467:MTMR1 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor