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Contents 1 Introduction to hormone-sensitive lipase 2 Structure of hormone-sensitive lipase 3 Inhibition of Hormone-Sensitive Lipase 4 Medical Relevance of Hormone-Sensitive Lipase 5 Additional Pages about Hormone-Sensitive Lipase 6 References

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. 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. ^[1]

Structure of hormone-sensitive lipase

spinqualitylabelsall models Hormone-Sensitive Lipase from 3dnm Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image 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. [2] The is comprised of Ser157, Glu251, and His281. The Ser157 residue sits at a site deemed the "nucleophile 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 .

Inhibition of Hormone-Sensitive Lipase

Medical Relevance of Hormone-Sensitive Lipase

Additional Pages about Hormone-Sensitive Lipase

• Lipase

References

1. ↑ 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/
2. ↑ 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