5CCW

Structure of the complex of a human telomeric DNA with Au(caffein-2-ylidene)2

Summary for 5CCW

• Entry DOI: 10.2210/pdb5ccw/pdb
• Descriptor: human telomeric DNA, POTASSIUM ION, Au(caffein-2-ylidene)2, ... (4 entities in total)
• Functional Keywords: drug-dna complex, g-quadruplex, drug/dna
• Biological source: Homo sapiens
• Total number of polymer chains: 1
• Total formula weight: 9206.09

Authors

Ferraroni, M.,Bazzicalupi, C.,Gratteri, P.,Messori, L.,Papi, F. (deposition date: 2015-07-02, release date: 2016-03-16, Last modification date: 2024-01-10)

Primary citation

Bazzicalupi, C.,Ferraroni, M.,Papi, F.,Massai, L.,Bertrand, B.,Messori, L.,Gratteri, P.,Casini, A.
Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investigation.
Angew.Chem.Int.Ed.Engl., 55:4256-4259, 2016

PubMed Abstract: The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)2 ]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines in vitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)2 ](+) and Tel 23 DNA G-quadruplex was solved. Tel 23 maintains a characteristic propeller conformation while binding three gold(I) dicarbene moieties at two distinct sites. Stacking interactions appear to drive noncovalent binding of the gold(I) complex. The structural basis for tight gold(I) complex/G-quadruplex recognition and its selectivity are described.

PubMed: 26929051
DOI: 10.1002/anie.201511999

Experimental method

X-RAY DIFFRACTION (1.89 Å)