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<StructureSection load='3DNM' size='350' frame='true' align='right' caption='Hormone-Sensitive Lipase from [[3dnm]]' scene='58/580297/3dnm_cartoon/2' > | <StructureSection load='3DNM' size='350' frame='true' align='right' caption='Hormone-Sensitive Lipase from [[3dnm]]' scene='58/580297/3dnm_cartoon/2' > | ||
| - | <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 [http://en.wikipedia.org/wiki/Catalytic_triad 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 [http://en.wikipedia.org/wiki/Catalytic_triad catalytic triad], a charge relay network that is characteristic of many hydrolases. 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 "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>. | 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>. | ||
Revision as of 00:20, 1 April 2014
Contents |
Introduction to hormone-sensitive lipase
Hormone-sensitive 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 catecholamines and inhibited by 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. [1]
Briefly, binding of catecholamines to β-adrenergic receptors coupled with adenylate cyclase (AC) stimulates G-proteins to increase the levels of cystolic cAMP. Elevated levels of cAMP leads to an activation 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. [2]
Structure of hormone-sensitive lipase
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Inhibition of hormone-sensitive lipase
Additional pages about hormone-sensitive lipase
References
- ↑ Yeaman SJ. Hormone-sensitive lipase--new roles for an old enzyme. Biochem J. 2004 Apr 1;379(Pt 1):11-22. PMID:14725507 doi:http://dx.doi.org/10.1042/BJ20031811
- ↑ Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans. 2003 Dec;31(Pt 6):1120-4. PMID:14641008 doi:http://dx.doi.org/10.1042/
- ↑ Nam KH, Kim MY, Kim SJ, Priyadarshi A, Kwon ST, Koo BS, Yoon SH, Hwang KY. Structural and functional analysis of a novel hormone-sensitive lipase from a metagenome library. Proteins. 2009 Mar;74(4):1036-40. PMID:19089974 doi:http://dx.doi.org/10.1002/prot.22313
