Sandbox Reserved 1091: Difference between revisions

ASP is a '''[http://en.wikipedia.org/wiki/Sepsis sepsis]-related factor'''. It can cause several dysfunctions like by inducing vascular leakage, reducing blood pressure via the activation of the [http://en.wikipedia.org/wiki/Kinin-kallikreinsystem kinin system] or promoting human plasma coagulation through the activation of [http://fr.m.wikipedia.org/wiki/Prothrombine prothrombin]. Finally, it can cause the formation of pus and edema through the action of anaphylatoxin C5a ([[4p3a]]). Gastroenteritis, and in extreme cases deuteropathy, are the main syndrome caused by infection with ''A.sobria''.

== Maturation ==

The '''ORF2 protein''' is composed of 152 amino-acids coded by the orf2 gene of 456 base pairs. The N-terminal extension and the C-terminal tail of the protein are implicated in the maturation of ASP. In fact, a complex ASP-ORF2 is formed. <ref>PMID:17951986</ref> This association requires a specific organization of ASP in the space. The sixth residue from the C-terminus domain of ORF2 interacts with the non-mature ASP. In the complex, the active site of ASP is blocked. This protects the protein from degradation by others.

When the complex is formed, it moves to the extracellular space and then it dissociates. The active ASP can dissociate ORF2 and exercise its virulence activity in the cell. <ref>Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities. Imamura T, Murakami Y, Nitta H. Biol. Chem. 398 1055-1068 (2017)</ref>

== Secondary structure ==

Moreover, there are <scene name='82/829344/Calcium_binding_sites/2'>Ca2+ Binding Sites</scene> in the ASP Structure (Ca1, Ca2 and Ca3). <scene name='82/829344/Ca1_et_ca2/4'>Ca1 and Ca2</scene> are situated in the N-terminal domain, while <scene name='82/829344/Ca3/3'>Ca3</scene> is situated in the C-terminal domain. These findings were assigned to ASP based on electron density, counter charges, and coordination.  

== Domains ==

All these domains are represented schematically in the article <ref>Structural Basis for the Kexin-like Serine Protease from Aeromonas sobria as Sepsis-causing Factor. H Kobayashi et al. J Biol Chem. 284(40): 27655–27663 (2009)</ref> : [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785694/figure/F2/ '''representation 2D of ASP''']. On these figures, we can see the different domains of the protein in A and also a superposition with the Kex2. We clearly see the resemblance between both serine protease, and the extra occluding region in the C-terminal region of ASP.

== Active site ==

The '''mechanism''' of the reaction is that the histidine will react with the serine and deprotonate it. The deprotonated hydroxyl group of the serine will act as a nucleophilic species and attack the carbon from the carbonyl function on the peptide. This will lead to the formation of a tetrahedral intermediate. The regeneration of the carbonyl group will be followed by the release of one part of the peptide, with an amine group at its extremity. Then, a second tetrahedral intermediate will be formed, but with the attack of a deprotonated water molecule. In the end, the regeneration of the active site will be done with the release of the part of the peptide with a carboxyl extremity. '''The polypeptide is also cut in two parts and the target protein isn't functional anymore'''. <ref>http://fr.wikipedia.org/wiki/Fichier:Serine_protease_mechanism_by_snellios.png</ref>A schematic representation of the mechanism with the involved amino acids can be found under the following link : [http://fr.wikipedia.org/wiki/Fichier:Serine_protease_mechanism_by_snellios.png '''mechanism of the reaction''' ]

== Properties ==

'''Antihistaminic agents''' ([http://en.wikipedia.org/wiki/Diphenhydramine diphenhydramine] and [http://en.wikipedia.org/wiki/Mepyramine pyrilamine]) were shown to efficiently inhibit vascular permeability enhancing the activity of the ASP. It is very likely that the vascular permeability enhancement is related to the release of [http://en.wikipedia.org/wiki/Histamine histamine] from [http://en.wikipedia.org/wiki/Mast_cell mast cells].

Through histopathological examinations it was shown that mast cells appeared around the injection site, confirming the role of histamine as a key factor.<ref>Physicochemical and biological properties od an extracellular serine protease od Aeromonas sobria. Ritsuko Yokoyama, Yoshio Fujii et al. Japan (2002)</ref>

== Impact on human body ==