Hormone sensitive lipase: Difference between revisions

[[Image:HPL_firstimage.png|300 px|left|thumb|Hormone-Sensitive Lipase from [[3dnm]]. Alpha helices and beta sheets are shown in red and yellow, respectively.]]

Hormone-sensitive [http://proteopedia.org/wiki/index.php/Lipase lipases] (HSL) represent a class of [http://en.wikipedia.org/wiki/Esterase esterases] within the [http://www.proteopedia.org/wiki/index.php/Hydrolase α/β hydrolase] family. HSL catalyzes the cleavage of ester bonds in fatty acid molecules when stimulated by a hormone.<ref name="Holm">PMID:14641008</ref> The activation and mobilization of hormone-sensitive lipase can be triggered by various [http://en.wikipedia.org/wiki/Catecholamine catecholamines] and inhibited by [http://www.proteopedia.org/wiki/index.php/Insulin insulin].<ref name= "Ray">PMID:12765952</ref> Catecholamines, such as [http://en.wikipedia.org/wiki/Epinephrine epinephrine], are rapidly spread throughout the body during times of energy mobilization, like in the [http://en.wikipedia.org/wiki/Fight-or-flight_response fight or flight response]. Conversely, insulin triggers glucose uptake, requiring the storage of energy, opposing HSL's function. HSL is clinically relevant, because the mobilization of or inability to mobilize fats in cells is directly related to fat accumulation seen in [http://en.wikipedia.org/wiki/Atherosclerosis artherosclerosis]and [http://en.wikipedia.org/wiki/Obesity obesity].<ref name= "Yeaman">PMID:14725507</ref>  Such diseases are characterized by an accumulation of fats and researchers are investigating whether HSL's activity plays a role or not.<ref name= "Ray">PMID:12765952</ref>  Investigation of HSL's structure and function could provide a better clinical understanding of these diseases.<ref name= "Yeaman">PMID:14725507</ref>  

<scene name='58/580297/3dnm_cartoon_dotsribbon/1'>Hormone-sensitive lipases</scene> are generally well-conserved across domains, including prokaryotes, showing 29, 26, and 22% residue overlap in [http://en.wikipedia.org/wiki/Alicyclobacillus ''Alicyclobacillus acidocaldarius''], [http://en.wikipedia.org/wiki/Archaeoglobus ''Archaeoglobus fulgidus''], and [http://en.wikipedia.org/wiki/Bacillus_subtilis ''Bacillus subtilis''], respectively.<ref name="Nam">PMID:19089974</ref>  HSL is composed of two main structural domains, consisting of a slightly variable N-terminus (shown in blue in the <scene name='58/580297/3dnm_cartoon/3'>default view</scene>) that is thought to contribute to numerous factors including activity, specificity, regioselectivity, thermophilicity, and thermostability.<ref name="Nam">PMID:19089974</ref> Research speculates that the N-terminal domain, consisting of about 300 residues, mediates protein-protein interactions, and possibly subsequent lipid binding.<ref name= "Yeaman">PMID:14725507</ref> The second domain of HSL is the C-terminal catalytic domain (colors other than blue), which contains serine residue phosphorylation sites as well as the [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad], viewed <scene name='58/580297/3dnm_triad_zoomedout/1'>here</scene> with ligand β-mercaptoethanol, a charge relay network that is characteristic of many hydrolases, such as [http://proteopedia.org/wiki/index.php/Chymotrypsin chymotrypsin].<ref name= "Yeaman">PMID:14725507</ref> With respect to sequence conservation across species, it has been shown that the catalytic domain, including the triad, is conserved across domains, but the domain containing the N-terminus shows little conservation.<ref name="Nam">PMID:19089974</ref> Size-exclusion chromatography studies have shown that HSL has a <scene name='58/580297/3dnm_cartoon_surface/4'>ligand pocket</scene> that is approximately 16Å deep, suggesting that HSL primarily hydrolyzes shorter chained molecules.<ref name="Nam">PMID:19089974</ref>

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