2KVY

NMR solution structure of the 4:1 complex between an uncharged distamycin A analogue and [d(TGGGGT)]4

Summary for 2KVY

• Entry DOI: 10.2210/pdb2kvy/pdb
• Descriptor: DNA (5'-D(*TP*GP*GP*GP*GP*T)-3'), 4-amino-1-methyl-N-{1-methyl-5-[(1-methyl-5-{[3-(methylamino)-3-oxopropyl]carbamoyl}-1H-pyrrol-3-yl)carbamoyl]-1H-pyrrol-3-yl}-1H-pyrrole-2-carboxamide (2 entities in total)
• Functional Keywords: g-quadruplex, coulombic interactions, nmr titration, distamycin a, structure calculations, isothermal titration calorimetry (itc), dna
• Total number of polymer chains: 4
• Total formula weight: 9395.04

Authors

Cosconati, S.,Marinelli, L.,Trotta, R.,Virno, A.,De Tito, S.,Romagnoli, R.,Pagano, B.,Limongelli, V.,Giancola, C.,Baraldi, P.,Mayol, L.,Novellino, E.,Randazzo, A. (deposition date: 2010-03-29, release date: 2010-05-26, Last modification date: 2024-05-22)

Primary citation

Cosconati, S.,Marinelli, L.,Trotta, R.,Virno, A.,De Tito, S.,Romagnoli, R.,Pagano, B.,Limongelli, V.,Giancola, C.,Baraldi, P.G.,Mayol, L.,Novellino, E.,Randazzo, A.
Structural and conformational requisites in DNA quadruplex groove binding: another piece to the puzzle.
J.Am.Chem.Soc., 132:6425-6433, 2010

PubMed Abstract: The study of DNA G-quadruplex stabilizers has enjoyed a great momentum in the late years due to their application as anticancer agents. The recognition of the grooves of these structural motifs is expected to result in a higher degree of selectivity over other DNA structures. Therefore, to achieve an enhanced knowledge on the structural and conformational requisites for quadruplex groove recognition, distamycin A, the only compound for which a pure groove binding has been proven, has been chemically modified. Surprisingly, structural and thermodynamic studies revealed that the absence of Coulombic interactions results in an unprecedented binding position in which both the groove and the 3' end of the DNA are occupied. This further contribution adds another piece to the so far elusive puzzle of the recognition between ligands and DNA quadruplexes and will serve as a platform for a rational design of new groove binders.

PubMed: 20394365
DOI: 10.1021/ja1003872

Experimental method

SOLUTION NMR