1YY0

Crystal structure of an RNA duplex containing a 2'-amine substitution and a 2'-amide product produced by in-crystal acylation at a C-A mismatch

Summary for 1YY0

• Entry DOI: 10.2210/pdb1yy0/pdb
• Descriptor: 5'-R(*GP*CP*AP*GP*AP*(A5M)P*UP*UP*AP*AP*AP*UP*CP*UP*GP*C)-3', 5'-R(*GP*CP*AP*GP*AP*(M5M)P*UP*UP*AP*AP*AP*UP*CP*UP*GP*C)-3', CALCIUM ION, ... (4 entities in total)
• Functional Keywords: 2'-amine, rna, duplex, mismatch, 2-amide, in-crystal reaction
• Total number of polymer chains: 3
• Total formula weight: 15365.47

Authors

Gherghe, C.M.,Krahn, J.M.,Weeks, K.M. (deposition date: 2005-02-23, release date: 2005-10-18, Last modification date: 2024-02-14)

Primary citation

Gherghe, C.M.,Krahn, J.M.,Weeks, K.M.
Crystal structures, reactivity and inferred acylation transition States for 2'-amine substituted RNA.
J.Am.Chem.Soc., 127:13622-13628, 2005

PubMed Abstract: Ribose 2'-amine substitutions are broadly useful as structural probes in nucleic acids. In addition, structure-selective chemical reaction at 2'-amine groups is a robust technology for interrogating local nucleotide flexibility and conformational changes in RNA and DNA. We analyzed crystal structures for several RNA duplexes containing 2'-amino cytidine (C(N)) residues that form either C(N)-G base pairs or C(N)-A mismatches. The 2'-amine substitution is readily accommodated in an A-form RNA helix and thus differs from the C2'-endo conformation observed for free nucleosides. The 2'-amide product structure was visualized directly by acylating a C(N)-A mismatch in intact crystals and is also compatible with A-form geometry. To visualize conformations able to facilitate formation of the amide-forming transition state, in which the amine nucleophile carries a positive partial charge, we analyzed crystals of the C(N)-A duplex at pH 5, where the 2'-amine is protonated. The protonated amine moves to form a strong electrostatic interaction with the 3'-phosphodiester. Taken together with solution-phase experiments, 2'-amine acylation is likely facilitated by either of two transition states, both involving precise positioning of the adjacent 3'-phosphodiester group.

PubMed: 16190727
DOI: 10.1021/ja053647y

Experimental method

X-RAY DIFFRACTION (3.2 Å)