Sandbox reserved 919: Difference between revisions
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[[Image:SURFACEINHIBITOR.png|300 px|left|thumb|Surface image of Hormone-Sensitive Lipase Complex with PMSF from [http://proteopedia.org/wiki/index.php/3h17 3h17]. Green indicates carbon atoms, blue indicates nitrogen atoms, red indicates oxygen atoms, and orange indicates sulfur atoms.]] | [[Image:SURFACEINHIBITOR.png|300 px|left|thumb|Surface image of Hormone-Sensitive Lipase Complex with PMSF from [http://proteopedia.org/wiki/index.php/3h17 3h17]. Green indicates carbon atoms, blue indicates nitrogen atoms, red indicates oxygen atoms, and orange indicates sulfur atoms.]] | ||
Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride ([http://en.wikipedia.org/wiki/PMSF PMSF]) covalently bound to the active site. The experiments performed to test this inhibition used different lipases obtained from [http://en.wikipedia.org/wiki/Bacillus_coagulans ''Bacillus coagulans''] as well as lipases from different areas of the human body. 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> The sulfur of PMSF binds to the oxygen of the hydroxyl group on the serine residue to form this covalent bond. This inhibitor will only bind to the active site of the catalytic serine because of its participation in the charge relay of the catalytic triad. This hyper activity, indicated by increased temperature (shown in red) around the active site <scene name='58/580296/Meshligand/3'>here</scene>, allows the sulfonyl group of PMSF to covalently bind to the catalytic serine residue to disrupt its activity. Because of this catalytic serine residue specificity, PMSF does not inhibit all kinds of lipases, such as [http://en.wikipedia.org/wiki/Pancreatic_lipase pancreatic lipase] and lipolase.<ref name="Kanwar">PMID:23923547</ref> PMSF is highly degradable in aqueous solutions as it has a [http://en.wikipedia.org/wiki/Half-life half-life] range of 35-110 minutes at [http://en.wikipedia.org/wiki/PH pH] levels of 7.0-8.0 <ref name="Gordon">PMID:26289</ref>. <scene name='58/580297/Pmsf_binding/2'>PMSF binding</scene> induces only a minor conformational change from the <scene name='58/580297/3dnm_ligandsite_triad_chains/7'>native protein</scene>. | Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride ([http://en.wikipedia.org/wiki/PMSF PMSF]) covalently bound to the <scene name='58/580297/Pmsf_surface/3'>active site</scene>. The experiments performed to test this inhibition used different lipases obtained from [http://en.wikipedia.org/wiki/Bacillus_coagulans ''Bacillus coagulans''] as well as lipases from different areas of the human body. 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> The sulfur of PMSF binds to the oxygen of the hydroxyl group on the serine residue to form this covalent bond. This inhibitor will only bind to the active site of the catalytic serine because of its participation in the charge relay of the catalytic triad. This hyper activity, indicated by increased temperature (shown in red) around the active site <scene name='58/580296/Meshligand/3'>here</scene>, allows the sulfonyl group of PMSF to covalently bind to the catalytic serine residue to disrupt its activity. Because of this catalytic serine residue specificity, PMSF does not inhibit all kinds of lipases, such as [http://en.wikipedia.org/wiki/Pancreatic_lipase pancreatic lipase] and lipolase.<ref name="Kanwar">PMID:23923547</ref> PMSF is highly degradable in aqueous solutions as it has a [http://en.wikipedia.org/wiki/Half-life half-life] range of 35-110 minutes at [http://en.wikipedia.org/wiki/PH pH] levels of 7.0-8.0 <ref name="Gordon">PMID:26289</ref>. <scene name='58/580297/Pmsf_binding/2'>PMSF binding</scene> induces only a minor conformational change from the <scene name='58/580297/3dnm_ligandsite_triad_chains/7'>native protein</scene>. | ||
Lack of regulation or increased activity of hormone-sensitive lipases can possibly lead to disorders such as atherosclerosis, obesity, and [http://en.wikipedia.org/wiki/Diabetes_mellitus#Type_2 type 2 diabetes]. Increased concentration of free fatty acids ([http://en.wikipedia.org/wiki/Fatty_acid#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.<ref name="Kraemer">PMID: 12364542 </ref> | Lack of regulation or increased activity of hormone-sensitive lipases can possibly lead to disorders such as atherosclerosis, obesity, and [http://en.wikipedia.org/wiki/Diabetes_mellitus#Type_2 type 2 diabetes]. Increased concentration of free fatty acids ([http://en.wikipedia.org/wiki/Fatty_acid#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.<ref name="Kraemer">PMID: 12364542 </ref> | ||
