Function
TrxR severs several functions inside the cell. One function of TrxR is to reduce compounds such as H2O2 which This protein's mechanism is greatly related to the orientation of the FAD and NADPH domains. The disulphide is then reduced to Trx-(SH)2 which is then used as a reducing agent for other compounds such as H2O2. Without the proper orientation of the two domains (FAD and NADPH) the electrons would not travel from NADPH to the FAD thus preventing the reaction completely.[3][4]
A second function of this protein is utilized in the regulation of DNA translation and in apoptosis. A normal stop codon (UGA, UAA, and UAG) stops the translation of the mRNA, but in the presence of TrxR an extra Selenocysteine is added to the end of the protein chain. This extra amino acid is what marks the structure for death inside the cell. Enough of these Selenocysteine structures in the cell and the entire cell will undergo apoptosis.[5]
Disease
When left unregulated cell death does not perform as functioned resulting in an accumulation of tissue and most often the cause of tumorous growths in the body. This tissue keeps living and dividing and without the TrxR to reduce H2O2 the radicals are able to run free through the cell destroying anything in their path. This would most likely lead to mutation or destruction of several parts of DNA which could lead to cell death, but more often than not would lead to cancerous growths.
Relevance
There needs to be be great surveillance on TrxR. Since the enzyme's action works specifically with cell death it needs to be highly regulated. Leaving TrxR unchecked could lead to too little or too much cell death. If TrxR is mutated or inhibited apoptosis is avoided tumors can form.
Targeting TrxR in cancer treatment is a new idea that hopefully will halt the growth of the cancer cell and cause it to self-destroy itself.[6]
Structural highlights
The catalytic site for TrxR is a -Cys-Val-Asn-Val-Gly-Cys- group that is located by the FAD site allowing for the easy transport of the extra electrons from the FAD and NADPH to the Thioredoxin present in the active site. When Thioredoxin enters the active site, the NADPH is oriented 66º off of the FAD and that allows electrons to transfer from the NADPH to the FAD and through that to the active site of the enzyme and the disulphide that resides there.
Part of the TrxR enzyme create a with itself creating crystals with which can be used to further study TrxR. This will hopefully to produce better anti-cancer drugs in the future.[7]
