Pseudomonas aeruginosa is Gram-negative bacteria. It is an opportunistic microorganism which established itself in vulnerable patients, like patients in intensive care units or those with cystic fibrosis. Pseudomonas aeruginosa is one of the major causes of Hospital-acquired infection worldwide and a serious threat to Public Health. [1]
Pseudomonas aeruginosa can colonize many natural environments like soil, water and skin, because of its ability to utilize a wide range of organic matter and cope with different environmental conditions. Pseudomonas aeruginosa colonizes human hosts, therefore it can use cysteine and methionine as sulfur source. [2]
Function
The thiol dioxygenation is the initial oxidation step which allow a thiol to catabolic and biosynthetic pathway. A family of specific non-heme mononuclear iron proteins catalyses the reaction. Each enzyme reacts efficiently with just one substrate. This family includes : cysteine dioxygenase, cysteamine dioxygenase, mercaptosuccinate dioxygenase and 3-mercaptopropionate dioxygenase. [3]
The thiol dioxygenase of Pseudomonas aeruginosa is a 3-mercaptopropionate dioxygenase (p3MDO) with a secondary cysteine dioxygenase activity. Therefore it can also be named 3-mercaptopropionate dioxygenase or cysteine dioxygenase.
This is the first exemple of cysteine dioxygenase homologue which utilizes a second substrate with near stochiometric coupling to dioxigen consumption.[4]
The cysteine dioxygenase homologue from Pseudomonas aeruginosa is expressed in low levels so this metabolic pathway is present in this organism.
The physiological role is unclear.
Interactions: Catalytic activity
The thiol dioxygenase catalyses the dioxygenation of 3-mercaptopropionate to 3-sulfinopropionate. [5]
Substrate often bounds to the ferrous iron through the thiol. However, spectroscopy indicates each substrate can bound differently to the enzyme. [6]
3-mercaptopropionate + O2 = 3-sulfinopropionate
It also oxidizes cysteine to cysteine sulfinate. [7]
Cysteine + O2 = Cysteine sulfinate
This enzyme has a marked preference for 3-mercaptopronionate, that’s why this enzyme is describe as a 3-mercaptopropionate dioxygenase.[8]
Image:Proteoppedia.jpg
Structural highlights
Thiol dioxygenases all share a common structure described as a 6-stranded β-barrel core, and a canonical cupin or “jelly roll” β-barrel that is formed with cupin motif 1, an intermotif region, and cupin motif 2 each forming two of the core six β-strands in the folded protein structure.[9]
The Thiol dioxygenase from Pseudomonas aeruginosa is made of 4 chains (named , , , )[10]. Each chain is made of 211 amino acids and has a molecular weight of 23 kDa. For its secondary structures, it has and [11]. The different binding sites with an atom of iron are three different Histidines : , and .
Furthermore, this proteins has two different domains which are a RmlC-like jelly roll fold and a RmlC-like cupin domain[12].
Disease
A mammalian cysteine dioxygenase also exists and its active site is slightly different, because of the replacement of an glutamine by a arginine. [13]
In humans, patients with a high level of cysteine and glutathione-cysteine mixed with disulphide are most likely to suffer from Hallervorden-Spatz (HS) syndrome which is essentially characterised by neurochemical abnormalities since it affects the globus pallidus.
Patients suffering from this disease have been observed to have a low level in cysteine dioxygenase activity.
Thus, in this case, cysteine accumulates locally in the globus palladus and the conversion of cysteine to taurine is blocked due to enzymatic inactivity.
An increasing amount of cysteine may increase the level of iron content in Hallervorden-Spatz disease and the additive effects of an accumulated amount of cysteine and of ferrous iron may give rise to the formation of free radicals that can damage neuronal membranes to cause the typical morphological changes observed in this disorder. [14]
