ISSN:
0948-5023
Keywords:
Keywords: P53-DNA interface
;
Mutation hotspots
;
VRML
;
1D + 3D structure analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The inactivation of the p53 tumor suppressor function by single missense point mutations is found in almost half of human tumors. Most p53 mutation hotspots are at the DNA binding interface, shown in the three-dimensional (3D) structure of a p53-DNA complex crystallized by Pavletich and coworkers [1]. We have investigated the influence of mutations on the predicted specific DNA binding capacities of p53 by using molecular modeling to compare biochemical properties of wild type and mutated p53 complexed to DNA. Changes in local properties e.g. electrostatic potential or hydrophilic/lipophilic properties, combined with the steric interferences, lead to a loss of specific binding and presumably disables the tumor suppressor function. The 3D-structures combined with molecular biochemical properties of the wild type and the mutated p53-DNA complex can be transferred by the use of the Virtual Reality Modeling Language (VRML). Special tools e.g. ′space buttons′ allow users the interactive exploration of structures, properties, and additional information via internet.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s0089470030382
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