Sandbox Reserved 1091: Difference between revisions
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This belonging to the subtilisin serine proteases family is hypothetical. Furthermore the predicted amino acid sequence reinforces this speculation. However, the size of the ASP (MW 65000) is unlike other subtilisin proteases (MW 30000). Also, the amino acid residues composition is different from the family’s characteristics because ASP shows unique cysteine residues that other family members don't show. Therefore we can state that it is likely that ASP belongs to the subtilisin serine proteases family, however it remains unclear. | This belonging to the subtilisin serine proteases family is hypothetical. Furthermore the predicted amino acid sequence reinforces this speculation. However, the size of the ASP (MW 65000) is unlike other subtilisin proteases (MW 30000). Also, the amino acid residues composition is different from the family’s characteristics because ASP shows unique cysteine residues that other family members don't show. Therefore we can state that it is likely that ASP belongs to the subtilisin serine proteases family, however it remains unclear. | ||
ASP was shown not to be a metalloprotease because its activity is not affected by metal chelators ([http://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid EDTA], [http://en.wikipedia.org/wiki/EGTA_(chemical) EGTA], [http://en.wikipedia.org/wiki/Phenanthroline o-phenanthroline]) or metalloprotease inhibitors ([http://en.wikipedia.org/wiki/Phosphoramidon phosphoramidon]). <ref>Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities. Takahisa Imamura et al. (2017)</ref> | ASP was shown not to be a metalloprotease because its activity is not affected by metal chelators ([http://en.wikipedia.org/wiki/Ethylenediaminetetraacetic_acid EDTA], [http://en.wikipedia.org/wiki/EGTA_(chemical) EGTA], [http://en.wikipedia.org/wiki/Phenanthroline o-phenanthroline]) or metalloprotease inhibitors ([http://en.wikipedia.org/wiki/Phosphoramidon phosphoramidon]). <ref>Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities. Takahisa Imamura et al. (2017)</ref> | ||
This protein is secreted by the Anaerobic bacterium [http://en.m.wikipedia.org/wiki/Aeromonas Aeromonas Sobria], which can cause potentially lethal [http://en.m.wikipedia.org/wiki/Septic_shock septic shock]. It is a clinical syndrome of potentially fatal organ dysfunction caused by a disorder in the response to infection. In septic shock, there is a critical reduction in tissue perfusion; acute multi visceral failure, including the lungs, kidneys and liver, can be observed. <ref>http://www.msdmanuals.com/professional/critical-care-medicine/sepsis-and-septic-shock/sepsis-and-septic-shock</ref> | This protein is secreted by the Anaerobic bacterium [http://en.m.wikipedia.org/wiki/Aeromonas Aeromonas Sobria], which can cause potentially lethal [http://en.m.wikipedia.org/wiki/Septic_shock septic shock]. It is a clinical syndrome of potentially fatal organ dysfunction caused by a disorder in the response to infection. In septic shock, there is a critical reduction in tissue perfusion; acute multi visceral failure, including the lungs, kidneys and liver, can be observed. <ref>http://www.msdmanuals.com/professional/critical-care-medicine/sepsis-and-septic-shock/sepsis-and-septic-shock</ref> | ||
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'''The catalytic triad:''' The [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] of ASP is composed of '''Asp78''', '''His115''' and '''Ser336'''. These amino acids are the base is the active site of the protein, where the mode of action of the serine protease takes place. A peptide can be inserted in the space of the active site. There, the amino acids of <scene name='82/829344/Catalytic_triad/2'>the catalytic triad</scene> will interact together and the mechanism will lead to a cut in the polypeptide. | '''The catalytic triad:''' The [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad] of ASP is composed of '''Asp78''', '''His115''' and '''Ser336'''. These amino acids are the base is the active site of the protein, where the mode of action of the serine protease takes place. A peptide can be inserted in the space of the active site. There, the amino acids of <scene name='82/829344/Catalytic_triad/2'>the catalytic triad</scene> will interact together and the mechanism will lead to a cut in the polypeptide. | ||
This triad can be observed in | This triad can be observed in a 2D representation of the protein : [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785694/figure/F3/ '''catalytic triad of ASP'''] | ||
'''Mechanism:''' The mechanism is the following: 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> | '''Mechanism:''' The mechanism of the reaction is the following : 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''' ] | 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''' ] | ||
