tailieunhanh - Báo cáo Y học: Two 1 : 1 binding modes for distamycin in the minor groove of d(GGCCAATTGG)

Single-crystal X-ray structure determinations of the complex between the minor-groove binder distamycin and d(GGCCAATTGG) reveal two 1 : 1 binding modes which differ in the orientation of the drug molecule in the minor groove. The two crystals were grown from different crystallization conditions and found to diffract to and ˚ A, respectively. The structures were refined to completion using SHELXL-93, resulting in a residual R factor of ˚ for the resolution structure (including 46 ˚ water molecules) and for the resolution structure (including 74 water molecules). . | Eur. J. Biochem. 269 2868-2877 2002 FEBS 2002 doi Two 1 1 binding modes for distamycin in the minor groove of d GGCCAATTGG Koen Uytterhoeven1 Jiri Sponer2 and Luc Van Meervelt1 1 Biomolecular Architecture Department of Chemistry Katholieke Universiteit Leuven Belgium 2Institute of Biophysics Academy of Sciences of the Czech Republic and National Center for Biomolecular Research Brno Czech Republic Single-crystal X-ray structure determinations of the complex between the minor-groove binder distamycin and d GGCCAATTGG reveal two 1 1 binding modes which differ in the orientation of the drug molecule in the minor groove. The two crystals were grown from different crystallization conditions and found to diffract to and A respectively. The structures were refined to completion using SHELXL-93 resulting in a residual R factor of for the resolution structure including 46 water molecules and for the resolution structure including 74 water molecules . In both orienta tions bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug and AT base pairs. VVÍlh a binding site of at least five base pairs close contacts between the terminal distamycin atoms and guanine amino groups are inevitable. The detailed nature of several of these interactions was further investigated by ab initio quantum chemical methods. Keywords distamycin drug-DNA complex minor groove binder quantum chemical calculations X-ray structure. Distamycin A Fig. 1 is a member of a family of naturally occuring oligopeptides showing antiviral and antibiotic properties. Like other minor-groove binder drugs distamy-cin binds noncovalently in the minor groove of DNA with a binding preference for stretches of AT-rich sequences 1 thereby preventing DNA and RNA synthesis by inhibition of the corresponding polymerase reaction. The crystal structure determination of a 1 1 distamycin-d CGCAAA TTTGCG complex 12-dista at A .