CRYSTAL-STRUCTURE OF THE PROMUTAGEN O-4-METHYLTHYMIDINE - IMPORTANCE OF THE ANTI CONFORMATION OF THE O(4) METHOXY GROUP AND POSSIBLE MISPAIRING OF O-4-METHYLTHYMIDINE WITH GUANINE

被引:27
作者
BRENNAN, RG
PYZALSKA, D
BLONSKI, WJP
HRUSKA, FE
SUNDARALINGAM, M
机构
[1] UNIV WISCONSIN, COLL AGR & LIFE SCI, DEPT BIOCHEM, MADISON, WI 53706 USA
[2] UNIV MANITOBA, DEPT CHEM, WINNIPEG R3T 2N2, MANITOBA, CANADA
关键词
D O I
10.1021/bi00353a036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
O4-Methylthymidine (O4medT) is a promutagen. To correlate its biological properties to changes in the electronic, geometric, and conformational properties of the pyrimidine base resulting from the keto to enol shift arising from methylation, an X-ray study of O4medT was undertaken. The crystal data are a = 4.950 (2) .ANG., b = 12.648 (1) .ANG., c = 19.305 (2) .ANG., space group P212121, Z = 4, and R = 0.042. The D-deoxyribofuranosyl ring is puckered in the uncommon 1T2 twist conformation with the phase angle of pseudorotation P = 133.8 (5).degree.. The amplitude of puckering .tau.m = 31.4 (3).degree. shows that the ring is considerably flattened. The base is in the anti conformation [.chi.CN = 40.6 (4).degree.], and the exocyclic C(4'').sbd.C(5'') bond (.PSI.) is gauche+ [46.2 (5).degree.]. Methylation produces cytosine-like conjugation for the thymine base. The methoxy group takes the syn-periplanar conformation. Two types of mispairings with guanine are possible, and both require the anti conformation for the O(4) methoxy group. Semiempirical energy calculations have been carried out and reveal that the anti conformation can be energetically assumed in the double helix by widening the exocyclic angles C(5).sbd.C(4).sbd.O(4) and C(4).sbd.C(5).sbd.C(7) and the angle C(4).sbd.O(4).sbd.C(8) at the methoxy group. Such coordinated expansion relieves unfavorable interactions between the C(7) and C(8) methyl groups.
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页码:1181 / 1185
页数:5
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