Summary information and primary citation
- PDB-id
-
101d;
SNAP-derived features in text and
JSON formats
- Class
- DNA
- Method
- X-ray (2.25 Å)
- Summary
- Refinement of netropsin bound to DNA: bias and feedback
in electron density map interpretation
- Reference
-
Goodsell DS, Kopka ML, Dickerson RE (1995): "Refinement
of netropsin bound to DNA: bias and feedback in electron
density map interpretation." Biochemistry,
34, 4983-4993. doi: 10.1021/bi00015a009.
- Abstract
- The X-ray crystal structure of the complex of the B-DNA
dodecamer CGCGAATTCGCG with the antitumor drug netropsin
has been reexamined to locate the drug accurately for
computer-based drug design. The optimum solution is with
the drug centered in the AATT region of the minor groove,
making three good bifurcated hydrogen bonds with adenine N3
and thymine O2 atoms along the floor of the groove. Pyrrole
rings of netropsin are packed against the C2 positions of
adenines, leaving no room for the amine group of guanine
and, hence, providing a structural rationale for the A.T
specificity of netropsin. An alternative positioning in
which the drug is shifted along the minor groove by ca.
one-half base pair step is rejected on the basis of free R
factor calculations and the appearance of the original
drug-free difference maps. Final omit maps, although of
more pleasing appearance, are not a dependable means of
discriminating between right and wrong structures. The
shifted alternative drug position ignores potential
hydrogen bonding along the floor of the groove, provides no
explanation for netropsin's observed A.T specificity, and
is contradicted by NMR results [Patel, D. J. (1982) Proc.
Natl. Acad. Sci. U.S.A. 79, 6424].
