Cargando…
Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity
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)P(2)) as substrates. Here, we determined the c...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809516/ https://www.ncbi.nlm.nih.gov/pubmed/27018598 http://dx.doi.org/10.1371/journal.pone.0152611 |
_version_ | 1782423650316582912 |
---|---|
author | Bong, Seoung Min Son, Kka-bi Yang, Seung-Won Park, Jae-Won Cho, Jea-Won Kim, Kyung-Tae Kim, Hackyoung Kim, Seung Jun Kim, Young Jun Lee, Byung Il |
author_facet | Bong, Seoung Min Son, Kka-bi Yang, Seung-Won Park, Jae-Won Cho, Jea-Won Kim, Kyung-Tae Kim, Hackyoung Kim, Seung Jun Kim, Young Jun Lee, Byung Il |
author_sort | Bong, Seoung Min |
collection | PubMed |
description | 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)P(2)) 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)(5)R motif of the active site. Additionally, our biochemical studies confirmed the substrate specificity of MTMR1 for PI(3)P and PI(3,5)P(2) over other phosphatidylinositol phosphates. Our structural and enzymatic analyses provide insight into the catalytic mechanism and biochemical properties of MTMR1. |
format | Online Article Text |
id | pubmed-4809516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48095162016-04-05 Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity Bong, Seoung Min Son, Kka-bi Yang, Seung-Won Park, Jae-Won Cho, Jea-Won Kim, Kyung-Tae Kim, Hackyoung Kim, Seung Jun Kim, Young Jun Lee, Byung Il PLoS One Research Article 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)P(2)) 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)(5)R motif of the active site. Additionally, our biochemical studies confirmed the substrate specificity of MTMR1 for PI(3)P and PI(3,5)P(2) over other phosphatidylinositol phosphates. Our structural and enzymatic analyses provide insight into the catalytic mechanism and biochemical properties of MTMR1. Public Library of Science 2016-03-28 /pmc/articles/PMC4809516/ /pubmed/27018598 http://dx.doi.org/10.1371/journal.pone.0152611 Text en © 2016 Bong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Bong, Seoung Min Son, Kka-bi Yang, Seung-Won Park, Jae-Won Cho, Jea-Won Kim, Kyung-Tae Kim, Hackyoung Kim, Seung Jun Kim, Young Jun Lee, Byung Il Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title | Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title_full | Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title_fullStr | Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title_full_unstemmed | Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title_short | Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity |
title_sort | crystal structure of human myotubularin-related protein 1 provides insight into the structural basis of substrate specificity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809516/ https://www.ncbi.nlm.nih.gov/pubmed/27018598 http://dx.doi.org/10.1371/journal.pone.0152611 |
work_keys_str_mv | AT bongseoungmin crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT sonkkabi crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT yangseungwon crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT parkjaewon crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT chojeawon crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT kimkyungtae crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT kimhackyoung crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT kimseungjun crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT kimyoungjun crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity AT leebyungil crystalstructureofhumanmyotubularinrelatedprotein1providesinsightintothestructuralbasisofsubstratespecificity |