C-H-RAS P21 protein catalytic domain (oncogenic G12V)
Homo sapiens (human)
Maybe the most prominent modern disease is cancer. Cancer is actually not a single disease, but a generic name for all kinds of diseases. In common to them all however is the uncontrolled growth of body cells. Probably a common cause of cancer is damages to the genetic material, the DNA, caused by oxidants. Oxidants produce free radicals, a highly chemically form of oxygen. Antioxidants, like vitamin C, can serve as sponges to absorb free radicals in the body. The result of free radicals is changes in the DNA sequence changing individual bases from one type to another. When such a sequence is expressed in the cell, these so-called point mutations lead to proteins with an incorrect sequence. In the case of the ras protein shown here the change of a single base of its gene produces a variant with an altered residue in position 12 of the amino acid sequence. Just as adenosine triphosphate (ATP) is the main source of chemical energy of cells, guanosine nucleotides like guanosine triphosphate (GTP) are often used as cellular signals to control chemical processes. ras is thought to play an important role in the control of cellular processes. It fulfills its function by hydrolyzing guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and phosphate (P).
The ras protein p21 shown here is the naturally occuring ras protein. An oncogenic ras21 has a mutation in residue 12 (see PDB:1Q21 for the wild type). It seems that this residue is important for the hydrolysis of GTP. It should be glycine and if it is anything else, then GTP is no longer properly hydrolyzed and ras p21 does not work as it should, resulting in a disruption of normal cellular processes.
Protein Data Bank (PDB)
author: Arno Paehler