Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

Mir, Aamir; Golden, Barbara L.

doi:10.1021/acs.biochem.5b01139

Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

Journal Article · Mon Nov 09 00:00:00 EST 2015 · Biochemistry

DOI:https://doi.org/10.1021/acs.biochem.5b01139· OSTI ID:1344904

Mir, Aamir ^[1]; Golden, Barbara L. ^[2]

Purdue Univ., West Lafayette, IN (United States); Office of Scientific and Technical Information (OSTI)
Purdue Univ., West Lafayette, IN (United States)

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 pK_A 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.

View Accepted Manuscript (DOE)

Research Organization:: Purdue Univ., West Lafayette, IN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1344904

Alternate ID(s):: OSTI ID: 1498408

Journal Information:: Biochemistry, Journal Name: Biochemistry Journal Issue: 4 Vol. 55; ISSN 0006-2960

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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