Drug Discovery Opinion

Hydrogen sulfide (H₂S) is best known for its characteristic smell of rotten eggs and for its toxicity, which is caused mainly by inhibition of mitochondrial respiration resulting from blockade of cytochrome oxidase. More recently, H₂S has been established as one of a number of gaseous signalling molecules, with roles in neuromodulation, smooth muscle relaxation, inflammation, insulin release and metabolic demand. Although biochemical pathways which generate H₂S have been elucidated, exactly what it does once generated has been unclear. Writing in the journal Science Signalling, a team led by researchers at Johns Hopkins University School of Medicine have now shown that H₂S converts cysteine residues to thiocysteines (ie modifies the –SH group to –SSH) in many liver proteins, including actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Interestingly, the cysteine residue in GAPDH that is modified to thiocysteine (Cys¹⁵⁰) is also a target of nitrosylation by nitric oxide (NO), another gaseous signalling molecule. Nitrosylation of the cysteine residue abolishes GAPDH activity, whereas conversion to thiocysteine augments activity, suggesting that the function of some proteins could be regulated by competitive nitrosylation or sulfhydration of the same cysteine residues. The extent of sulfhydration (10-25%) is considerably higher than the degree of protein S-nitrosylation thought to occur physiologically.

Related posts:

1. Still Signalling from Below the Surface Compounds acting at G-protein coupled receptors (GPCRs) form the largest class of drug molecules but, although the biochemical steps involved...
2. Insulin Growth Factor Signalling in Alzheimer’s Disease Although family history and lifestyle choices play a role, ageing is recognised to be the largest single risk factor...
3. Histamine Signalling in Cerebral Malaria Histamine is a biogenic amine which acts as a mediator of immune responses as well as acting as a neurotransmitter...
4. Hydrogen Sulphide Important in Blood Pressure Control The concept of gaseous molecules as signalling messengers began to emerge in the 1980s with the discovery of endothelial derived...
5. Mapping Phosphorylation in Cancer Phosphorylation is a key mechanism for regulation of protein activity and the phosphorylation of tyrosine residues, in particular, is important...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Tuesday, November 17th, 2009 at 8:43 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.