DNA repair enzyme
Homo sapiens (human)
DNA stores the genetic information in a long linear double strand of nucleotides. The alternating sequence of the four bases that occur in DNA contains all that is necessary to encode the information about the sequence of proteins. A specific sequence of 3 base pairs encodes one kind of amino acid. When bases are damaged, the protein production machinery of the cell can no longer produce the correct protein and when a copy of the DNA is made the new copy will also contain errors. Damage to DNA can occur by various means. One is UV or other energetic radiation that leads to the formation of dimers between adjacent bases. Other sources of damage may be chemical reactions that modify bases. The cell produces various enzymes whose duty is to identify errors in DNA, cut out erroneous bases and replace them with correct bases. The first step of this cycle is the identification of damaged bases. Since the cell contains many bases, this identification must be accurate and distinguish between normal and damaged bases.
The protein shown here is an example of one such damaged base hunter. The structure shows the protein and a piece of DNA which contains a damaged base. A loop that connects two strand of an antiparallel beta-sheet sticks into the DNA almost like a crowbar forcing the damaged base out of its normal orientation. The base pairs directly neighboring the damaged base are almost unaffected by this large motion of the damage base. The damaged base itself is buried inside a deep pocket on the surface of the protein. Once it is properly oriented, the protein will then cut the bond that connects the erroneous base to the sugar-phosphate backbone of the DNA and other enzymes can proceed to insert a correct base in its stead.
Protein Data Bank (PDB)
Lau, A.Y. Wyatt, M.D. Glassner, B.J. Samson, L.D. Ellenberger, T.; "Molecular basis for discriminating between normal and damaged bases by the human alkyladenine glycosylase, AAG."; Proc. Natl. Acad. Sci. U.S.A.; (2000) 97:13573-13578 PubMed:11106395.
author: Arno Paehler