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


Authors: Lin, C. H.; Wang, W.; Jones, R. A.; Patel, D. J.
Article Title: Formation of an amino-acid-binding pocket through adaptive zippering-up of a large DNA hairpin loop
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.
Keywords: protein binding; dna; guanine; ligand; magnetic resonance spectroscopy; base sequence; base pairing; hydrogen bond; models, molecular; molecular structure; amino acids; nucleic acid conformation; arginine; nitrogen isotopes; in vitro selection; base pair mismatch; guanidine; cytosine; dna aptamer; argininamide; adaptive dna structural transitions; l-argininamide-binding pocket; minor-groove base encapsulation; sheared g · a triple alignments; dna hairpin loop
Journal Title: Chemistry and Biology
Volume: 5
Issue: 10
ISSN: 1074-5521
Publisher: Elsevier Inc.  
Date Published: 1998-10-01
Start Page: 555
End Page: 572
Language: English
PUBMED: 9818148
PROVIDER: scopus
DOI: 10.1016/S1074-5521(98)90114-4
DOI/URL:
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Chin H Lin
    9 Lin
  2. Dinshaw J Patel
    445 Patel