Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue
Abstract
The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. Finally, on the basis of this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.
- Authors:
-
- Purdue Univ., West Lafayette, IN (United States)
- Publication Date:
- Research Org.:
- Purdue Univ., West Lafayette, IN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1344904
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Biochemistry
- Additional Journal Information:
- Journal Volume: 55; Journal Issue: 4; Journal ID: ISSN 0006-2960
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Citation Formats
Mir, Aamir, and Golden, Barbara L. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue. United States: N. p., 2015.
Web. doi:10.1021/acs.biochem.5b01139.
Mir, Aamir, & Golden, Barbara L. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue. United States. https://doi.org/10.1021/acs.biochem.5b01139
Mir, Aamir, and Golden, Barbara L. Mon .
"Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue". United States. https://doi.org/10.1021/acs.biochem.5b01139. https://www.osti.gov/servlets/purl/1344904.
@article{osti_1344904,
title = {Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue},
author = {Mir, Aamir and Golden, Barbara L.},
abstractNote = {The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. Finally, on the basis of this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.},
doi = {10.1021/acs.biochem.5b01139},
journal = {Biochemistry},
number = 4,
volume = 55,
place = {United States},
year = {Mon Nov 09 00:00:00 EST 2015},
month = {Mon Nov 09 00:00:00 EST 2015}
}
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