Water-Bridge Mediates Recognition of mRNA Cap in eIF4E
Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5′ mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which a...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/84992 http://hdl.handle.net/10220/42071 |
| _version_ | 1811689897545695232 |
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| author | Lama, Dilraj Pradhan, Mohan R. Brown, Christopher J. Eapen, Rohan S. Joseph, Thomas L. Kwoh, Chee-Keong Lane, David P. Verma, Chandra Shekhar |
| author2 | School of Computer Science and Engineering |
| author_facet | School of Computer Science and Engineering Lama, Dilraj Pradhan, Mohan R. Brown, Christopher J. Eapen, Rohan S. Joseph, Thomas L. Kwoh, Chee-Keong Lane, David P. Verma, Chandra Shekhar |
| author_sort | Lama, Dilraj |
| collection | NTU |
| description | Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5′ mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which also persist in molecular dynamics simulations. These waters engage an intricate hydrogen-bond network between the cap and protein. Two crystallographic waters in the cleft of the pocket show a high degree of conservation and bridge two residues, which are part of an evolutionarily conserved scaffold. This appears to be a preformed recognition module for the cap with the two structural waters facilitating an efficient interaction. This is also recapitulated in a new crystal structure of the apo protein. These findings open new windows for the design and screening of compounds targeting eIF4E. |
| first_indexed | 2024-10-01T05:55:24Z |
| format | Journal Article |
| id | ntu-10356/84992 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:55:24Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/849922020-03-07T11:48:53Z Water-Bridge Mediates Recognition of mRNA Cap in eIF4E Lama, Dilraj Pradhan, Mohan R. Brown, Christopher J. Eapen, Rohan S. Joseph, Thomas L. Kwoh, Chee-Keong Lane, David P. Verma, Chandra Shekhar School of Computer Science and Engineering School of Biological Sciences Translation initiation factor 4E protein 5′ mRNA cap Ligand binding pockets in proteins contain water molecules, which play important roles in modulating protein-ligand interactions. Available crystallographic data for the 5′ mRNA cap-binding pocket of the translation initiation factor protein eIF4E shows several structurally conserved waters, which also persist in molecular dynamics simulations. These waters engage an intricate hydrogen-bond network between the cap and protein. Two crystallographic waters in the cleft of the pocket show a high degree of conservation and bridge two residues, which are part of an evolutionarily conserved scaffold. This appears to be a preformed recognition module for the cap with the two structural waters facilitating an efficient interaction. This is also recapitulated in a new crystal structure of the apo protein. These findings open new windows for the design and screening of compounds targeting eIF4E. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version 2017-02-03T08:43:31Z 2019-12-06T15:55:03Z 2017-02-03T08:43:31Z 2019-12-06T15:55:03Z 2017 Journal Article Lama, D., Pradhan, M. R., Brown, C. J., Eapen, R. S., Joseph, T. L., Kwoh, C. -K., et al. (2017). Water-Bridge Mediates Recognition of mRNA Cap in eIF4E. Structure, 25(1), 188-194. 0969-2126 https://hdl.handle.net/10356/84992 http://hdl.handle.net/10220/42071 10.1016/j.str.2016.11.006 en Structure © 2016 Elsevier Ltd. This is the author created version of a work that has been peer reviewed and accepted for publication by Structure, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.str.2016.11.006]. 22 p. application/pdf |
| spellingShingle | Translation initiation factor 4E protein 5′ mRNA cap Lama, Dilraj Pradhan, Mohan R. Brown, Christopher J. Eapen, Rohan S. Joseph, Thomas L. Kwoh, Chee-Keong Lane, David P. Verma, Chandra Shekhar Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title | Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title_full | Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title_fullStr | Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title_full_unstemmed | Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title_short | Water-Bridge Mediates Recognition of mRNA Cap in eIF4E |
| title_sort | water bridge mediates recognition of mrna cap in eif4e |
| topic | Translation initiation factor 4E protein 5′ mRNA cap |
| url | https://hdl.handle.net/10356/84992 http://hdl.handle.net/10220/42071 |
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