6J0I

Structure of [Co2+-(Chromomycin A3)2]-d(TTGGCGAA)2 complex

Summary for 6J0I

• Entry DOI: 10.2210/pdb6j0i/pdb
• Descriptor: DNA (5'-D(*TP*TP*GP*GP*CP*GP*AP*A)-3'), 2,6-dideoxy-4-O-methyl-alpha-D-galactopyranose-(1-3)-(2R,3R,6R)-6-hydroxy-2-methyltetrahydro-2H-pyran-3-yl acetate, 3-C-methyl-4-O-acetyl-alpha-L-Olivopyranose-(1-3)-(2R,5S,6R)-6-methyltetrahydro-2H-pyran-2,5-diol-(1-3)-(2R,5S,6R)-6-methyltetrahydro-2H-pyran-2,5-diol, ... (6 entities in total)
• Functional Keywords: mismatch dna, chromomycin a3, drug-dna complex, g:g mismatch, dna-antibiotic complex, dna/antibiotic
• Biological source: synthetic construct
• Total number of polymer chains: 6
• Total formula weight: 22048.06

Authors

Satange, R.B.,Chuang, C.Y.,Hou, M.H. (deposition date: 2018-12-24, release date: 2019-07-24, Last modification date: 2023-11-22)

Primary citation

Satange, R.,Chuang, C.Y.,Neidle, S.,Hou, M.H.
Polymorphic G:G mismatches act as hotspots for inducing right-handed Z DNA by DNA intercalation.
Nucleic Acids Res., 47:8899-8912, 2019

PubMed Abstract: DNA mismatches are highly polymorphic and dynamic in nature, albeit poorly characterized structurally. We utilized the antitumour antibiotic CoII(Chro)2 (Chro = chromomycin A3) to stabilize the palindromic duplex d(TTGGCGAA) DNA with two G:G mismatches, allowing X-ray crystallography-based monitoring of mismatch polymorphism. For the first time, the unusual geometry of several G:G mismatches including syn-syn, water mediated anti-syn and syn-syn-like conformations can be simultaneously observed in the crystal structure. The G:G mismatch sites of the d(TTGGCGAA) duplex can also act as a hotspot for the formation of alternative DNA structures with a GC/GA-5' intercalation site for binding by the GC-selective intercalator actinomycin D (ActiD). Direct intercalation of two ActiD molecules to G:G mismatch sites causes DNA rearrangements, resulting in backbone distortion to form right-handed Z-DNA structures with a single-step sharp kink. Our study provides insights on intercalators-mismatch DNA interactions and a rationale for mismatch interrogation and detection via DNA intercalation.

PubMed: 31361900
DOI: 10.1093/nar/gkz653

Experimental method

X-RAY DIFFRACTION (2.5 Å)