Formation of an amino-acid-binding pocket through adaptive zippering-up of a large DNA hairpin loop

Chin H. Lin, Weimin Wang, Roger A. Jones, Dinshaw J. Patel

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Background: In vitro selection has identified DNA aptamers that target cofactors, amino acids, peptides and proteins. Structure determination of such ligand-DNA aptamer complexes should elucidate the details of adaptive DNA structural transitions, binding-pocket architectures and ligand recognition. We have determined the solution structure of the complex of a DNA aptamer containing a guanine-rich 18-residue hairpin loop that binds L-argininamide with ~ 100μM affinity. Results: The DNA aptamer generates its L-argininamide-binding pocket by adaptive zippering up the 18-residue loop through formation of watson-Crick pairs, mismatch pairs and base triples, while maximizing stacking interactions. Three of the four base triples involve minor-groove recognition through sheared G · A mismatch formation. The unique fold is also achieved through positioning of an adenine residue deep within the minor groove and through nestling of a smaller loop within the larger loop on complex formation. The accessibility to the unique L-argininamide-binding pocket is restricted by a base pair that bridges across one side of the major-groove-binding site. The guanidinium group of the bound L-argininamide aligns through intermolecular hydrogen-bond formation with the base edges of nonadjacent guanine and cytosine residues while being sandwiched between the planes of nonadjacent guanine residues. Conclusions: The available structures of L-arginine/L-argininamide bound to their DNA and RNA targets define the common principles and patterns associated with molecular recognition, as well as the diversity of intermolecular hydrogen-bonding alignments associated with the distinct binding pockets.

Original languageEnglish (US)
Pages (from-to)555-572
Number of pages18
JournalChemistry and Biology
Volume5
Issue number10
DOIs
StatePublished - Oct 1998

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Keywords

  • Adaptive DNA structural transitions
  • L-argininamide-binding pocket
  • Minor-groove base encapsulation
  • Sheared G · A triple alignments

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