Sandbox reserved 919: Difference between revisions
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[[Image:HPL_Movie0006.png|300 px|left|thumb|Hormone-Sensitive Lipase]] | [[Image:HPL_Movie0006.png|300 px|left|thumb|Hormone-Sensitive Lipase]] | ||
Hormone-sensitive [http://proteopedia.org/wiki/index.php/Lipase lipases] (HSL) represent a class of esterases within the hydrolase family that catalyzes the cleavage of ester bonds in fatty acid molecules when stimulated by a hormone. The activation and mobilization of these hormone-sensitive lipases can be triggered by various [http://en.wikipedia.org/wiki/Catecholamine catecholamines] and inhibited by [http://www.proteopedia.org/wiki/index.php/Insulin insulin]. Briefly, binding of catecholamines to β-adrenergic receptors coupled with [http://www.proteopedia.org/wiki/index.php/Adenylate_Cyclase adenylate cyclase] (AC) stimulates G-proteins to increase the levels of cystolic [http://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cAMP]. Elevated levels of cAMP leads to an activation [http://www.proteopedia.org/wiki/index.php/Protein_kinase_A protein kinase A] (PKA) leading to phosphorylation of serine residues on HSL activating and translocating HSL to lipid droplets for lipolysis. Conversely, insulin signaling decreases cystolic cAMP levels, resulting in a decreased HSL mobilization. <ref name="Holm">PMID:14641008</ref> | Hormone-sensitive [http://proteopedia.org/wiki/index.php/Lipase lipases] (HSL) represent a class of esterases within the hydrolase family that catalyzes the cleavage of ester bonds in fatty acid molecules when stimulated by a hormone. The activation and mobilization of these hormone-sensitive lipases can be triggered by various [http://en.wikipedia.org/wiki/Catecholamine catecholamines] and inhibited by [http://www.proteopedia.org/wiki/index.php/Insulin insulin]. HSL is clinically relevant because the mobilization of fats in cells is directly related to fat accumulation seen in atherosclerosis, diabetes, and obesity. Investigation of HSL's structure and function could provide a better clinical understanding of these diseases. <ref name= "Yeaman">PMID:14725507</ref> | ||
Briefly, binding of catecholamines to β-adrenergic receptors coupled with [http://www.proteopedia.org/wiki/index.php/Adenylate_Cyclase adenylate cyclase] (AC) stimulates G-proteins to increase the levels of cystolic [http://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cAMP]. Elevated levels of cAMP leads to an activation [http://www.proteopedia.org/wiki/index.php/Protein_kinase_A protein kinase A] (PKA) leading to phosphorylation of serine residues on HSL activating and translocating HSL to lipid droplets for lipolysis. Conversely, insulin signaling decreases cystolic cAMP levels, resulting in a decreased HSL mobilization. <ref name="Holm">PMID:14641008</ref> | |||
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<scene name='58/580297/3dnm_cartoon/2'>Hormone-sensitive lipases</scene> are generally well-conserved across species. HSL is composed of two main structural domains, consisting of a slightly variable N-terminus that is thought to contribute to numerous factors including activity, specificity, regioselectivity, thermophilicity, and thermostability. The second, highly conserved, domain of HSL is the C-terminal catalytic domain, which contains the catalytic triad. Size-exclusion chromatography studies have shown that HSL has a ligand pocket that is approximately 16Å deep, suggesting that HSL primarily hydrolyzes shorter chained molecules. <ref name="Nam">PMID:19089974</ref> | <scene name='58/580297/3dnm_cartoon/2'>Hormone-sensitive lipases</scene> are generally well-conserved across species. HSL is composed of two main structural domains, consisting of a slightly variable N-terminus that is thought to contribute to numerous factors including activity, specificity, regioselectivity, thermophilicity, and thermostability. The second, highly conserved, domain of HSL is the C-terminal catalytic domain, which contains the catalytic triad. Size-exclusion chromatography studies have shown that HSL has a ligand pocket that is approximately 16Å deep, suggesting that HSL primarily hydrolyzes shorter chained molecules. <ref name="Nam">PMID:19089974</ref> | ||
The <scene name='58/580297/3dnm_ligandsite_charge_relay/1'>catalytic triad</scene> is comprised of Ser157, Glu251, and His281. The Ser157 residue sits at a site deemed the " | The <scene name='58/580297/3dnm_ligandsite_charge_relay/1'>catalytic triad</scene> is comprised of Ser157, Glu251, and His281. The Ser157 residue sits at a site deemed the "nucleophilic elbow," that models an approximate torsion of Φ = 60° and Ψ =-120°. This nucleophilic elbow is stabilized by a hydrogen bond between the proximal nitrogen and oxygen atoms of His281 and Glu251, respectively. This model also shows the Ser157 residue to be stabilized by the covalent binding of <scene name='58/580297/3dnm_cartoon_ligand/2'>β-mercaptoethanol</scene>. | ||
</StructureSection> | </StructureSection> | ||
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==Additional Pages about Hormone-Sensitive Lipase== | ==Additional Pages about Hormone-Sensitive Lipase== | ||
* [http://en.wikipedia.org/wiki/Hormone_sensitive_lipase] | |||
* [http://proteopedia.org/wiki/index.php/Lipase Lipase] | * [http://proteopedia.org/wiki/index.php/Lipase Lipase] | ||
* [] | |||
==References== | ==References== | ||
<references /> | <references /> | ||
