2. Academic Validation
  3. Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity

Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity

  • PLoS One. 2016 Mar 28;11(3):e0152611. doi: 10.1371/journal.pone.0152611.
Seoung Min Bong 1,  Kka-bi Son 2,  Seung-Won Yang 1,  Jae-Won Park 1,  Jea-Won Cho 1,  Kyung-Tae Kim 1,  Hackyoung Kim 2,  Seung Jun Kim 3,  Young Jun Kim 2,  Byung Il Lee 1
Affiliations

Affiliations

  • 1 Research institute, National Cancer Center, Goyang, Gyeonggi 10408, Republic of Korea.
  • 2 Department of Biomedical Chemistry, Konkuk University, Chungju 27478, Republic of Korea.
  • 3 Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
PMID: 27018598 DOI: 10.1371/journal.pone.0152611
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.

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