The GlcN6P cofactor plays multiple catalytic roles in the glmS ribozyme

Jamie L. Bingaman, Sixue Zhang, David R. Stevens, Neela H. Yennawar, Sharon Hammes-Schiffer, Philip C. Bevilacqua

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

RNA enzymes (ribozymes) have remarkably diverse biological roles despite having limited chemical diversity. Protein enzymes enhance their reactivity through recruitment of cofactors; likewise, the naturally occurring glmS ribozyme uses the glucosamine-6-phosphate (GlcN6P) organic cofactor for phosphodiester bond cleavage. Prior structural and biochemical studies have implicated GlcN6P as the general acid. Here we describe new catalytic roles of GlcN6P through experiments and calculations. Large stereospecific normal thio effects and a lack of metal-ion rescue in the holoribozyme indicate that nucleobases and the cofactor play direct chemical roles and align the active site for self-cleavage. Large stereospecific inverse thio effects in the aporibozyme suggest that the GlcN6P cofactor disrupts an inhibitory interaction of the nucleophile. Strong metal-ion rescue in the aporibozyme reveals that this cofactor also provides electrostatic stabilization. Ribozyme organic cofactors thus perform myriad catalytic roles, thereby allowing RNA to compensate for its limited functional diversity.

Original languageEnglish (US)
Pages (from-to)439-445
Number of pages7
JournalNature Chemical Biology
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The GlcN6P cofactor plays multiple catalytic roles in the glmS ribozyme'. Together they form a unique fingerprint.

Cite this