1ztt
Netropsin bound to d(CTTAATTCGAATTAAG) in complex with MMLV RT catalytic fragment
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OverviewOverview
Netropsin is a well-characterized DNA minor groove binding compound that, serves as a model for the study of drug-DNA interactions. Our laboratory, has developed a novel host-guest approach to study drug-DNA interactions, in which the host, the N-terminal fragment of Moloney murine leukemia, virus reverse transcriptase (MMLV RT) is co-crystallized with a DNA, oligonucleotide guest in the presence and absence of drug. We have, co-crystallized netropsin with the RT fragment bound to the symmetric, 16mer d(CTTAATTCGAATTAAG)2 and determined the structure of the complex at, 1.85 A. In contrast to previously reported netropsin-DNA structures, our, oligonucleotide contains two AATT sites that bind netropsin with flanking, 5' and 3' sequences that are not symmetric. The asymmetric unit of the RT, fragment-DNA-netropsin crystals contains one protein molecule and one-half, of the 16mer with one netropsin molecule bound. The guanidinium moiety of, netropsin binds in a narrow part of the minor groove, while the amidinium, is bound in the widest region within the site. We compare this structure, to other Class I netropsin-DNA structures and find that the asymmetry of, minor groove widths in the AATT site contributes to the orientation of, netropsin within the groove while hydrogen bonding patterns vary in the, different structures.
About this StructureAbout this Structure
1ZTT is a Single protein structure of sequence from Moloney murine leukemia virus with NT as ligand. Active as RNA-directed DNA polymerase, with EC number 2.7.7.49 Full crystallographic information is available from OCA.
ReferenceReference
A host-guest approach for determining drug-DNA interactions: an example using netropsin., Goodwin KD, Long EC, Georgiadis MM, Nucleic Acids Res. 2005 Jul 27;33(13):4106-16. Print 2005. PMID:16049022
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