Sandbox reserved 919: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 25: | Line 25: | ||
Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride ([http://en.wikipedia.org/wiki/PMSF PMSF]) covalently bound to the <scene name='58/580296/Meshligand/2'>active site</scene>. The experiments performed to test this inhibition used different strains of bacteria, which had a different order of residues but the same catalytic effect. This experiment tested the catalytic serine residue rather than the Ser157 residue seen in other HSL proteins. PMSF inhibits hydrolase by binding to the catalytic serine residue of the [http://proteopedia.org/wiki/index.php/Serine_Proteases serine protease] active site which disrupts the nucleophilic activity of the catalytic serine.<ref name="Kim">PMID: 19715665 </ref> This inhibitor will only bind to the active site Ser144 because of its participation in the charge relay of the <scene name='58/580296/Meshligandinteraction/1'>catalytic triad</scene>. This hyper activity allows the sulfonyl group of PMSF to <scene name='58/580296/Inhibitorinteraction/4'>covalently bond</scene> to the catalytic serine residue to disrupt its activity. Because of this catalytic serine residue specificity, PMSF does not inhibit all kinds of lipases, lipases such as pancreatic lipase and lipolase will not be inhibited by PMSF.<ref name="Kanwar">PMID:23923547</ref> PMSF is highly degradable in aqueous solutions so it does not inhibit for very long periods of time in its natural environment. PMSF binding induces only a minor conformational change from the native protein.<ref name="Kanwar"> | Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride ([http://en.wikipedia.org/wiki/PMSF PMSF]) covalently bound to the <scene name='58/580296/Meshligand/2'>active site</scene>. The experiments performed to test this inhibition used different strains of bacteria, which had a different order of residues but the same catalytic effect. This experiment tested the catalytic serine residue rather than the Ser157 residue seen in other HSL proteins. PMSF inhibits hydrolase by binding to the catalytic serine residue of the [http://proteopedia.org/wiki/index.php/Serine_Proteases serine protease] active site which disrupts the nucleophilic activity of the catalytic serine.<ref name="Kim">PMID: 19715665 </ref> This inhibitor will only bind to the active site Ser144 because of its participation in the charge relay of the <scene name='58/580296/Meshligandinteraction/1'>catalytic triad</scene>. This hyper activity allows the sulfonyl group of PMSF to <scene name='58/580296/Inhibitorinteraction/4'>covalently bond</scene> to the catalytic serine residue to disrupt its activity. Because of this catalytic serine residue specificity, PMSF does not inhibit all kinds of lipases, lipases such as pancreatic lipase and lipolase will not be inhibited by PMSF.<ref name="Kanwar">PMID:23923547</ref> PMSF is highly degradable in aqueous solutions so it does not inhibit for very long periods of time in its natural environment. PMSF binding induces only a minor conformational change from the native protein.<ref name="Kanwar"> | ||
Lack of regulation or increased activity of hormone-sensitive lipases can possibly lead to disorders such as atherosclerosis, obesity, and type 2 diabetes. Increased concentration of free fatty acids (FFA) in skeletal muscles has been reported in many cases of obesity and type 2 diabetes. Inability to regulate or insufficient inhibition of HSL by PMSF could, in theory, also be a possible cause of these diseases. | |||
</StructureSection> | </StructureSection> | ||
