Sandbox 78: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
HGL, a dimeric enzyme consisting of two 379 amino acid residue-long subunits, possesses a <scene name='72/728060/Catalytic_elbow/3'>Catalytic Arm</scene> consisting of residues Ser-153, His-353, and Asp-324 essential to the breakdown of lipids, coordinated with an oxyanion hole Leu-67 Gln-154 <ref name="dogs">PMID:20965171</ref>, that serves to stabilize the transition state. Structurally, the human gastric lipase exhibits a complex, <scene name='72/728060/Secondary_structure/1'>Secondary Structure</scene>, where the "lid", residues 215-244 <ref name="dogs">PMID:20965171</ref>, of the lipase gives way to the <scene name='72/728060/Hydrophobic_regions/1'>Hydrophobic Areas</scene> (hydrophobic regions noted in red) both surrounding the active site and interfacing the lid, thought to draw lipids and promote docking <ref name="roussel" />. | HGL, a dimeric enzyme consisting of two 379 amino acid residue-long subunits, possesses a <scene name='72/728060/Catalytic_elbow/3'>Catalytic Arm</scene> consisting of residues Ser-153, His-353, and Asp-324 essential to the breakdown of lipids, coordinated with an oxyanion hole Leu-67 Gln-154 <ref name="dogs">PMID:20965171</ref>, that serves to stabilize the transition state. Structurally, the human gastric lipase exhibits a complex, <scene name='72/728060/Secondary_structure/1'>Secondary Structure</scene> (beta sheets shown in yellow, alpha helices shown in orange, coiled coils shown in green, and amino acid side chains shown as purple), where the "lid", residues 215-244 <ref name="dogs">PMID:20965171</ref>, of the lipase gives way to the <scene name='72/728060/Hydrophobic_regions/1'>Hydrophobic Areas</scene> (hydrophobic regions noted in red) both surrounding the active site and interfacing the lid, thought to draw lipids and promote docking <ref name="roussel" />. | ||
== Function == | == Function == | ||
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[[Image:Hydrolysis triacylglycerol reaction.png|400px|left|thumb| Hydrolysis of triacylglycerol. This reaction is catalyzed by HGL.]] | [[Image:Hydrolysis triacylglycerol reaction.png|400px|left|thumb| Hydrolysis of triacylglycerol. This reaction is catalyzed by HGL.]] | ||
HGL functions at an optimal pH of approximately five, and primarily catalyzes the hydrolysis of short-chain triacylglycerols <ref name="kinetic assay">PMID: | HGL functions at an optimal pH of approximately five, and primarily catalyzes the hydrolysis of short-chain triacylglycerols <ref name="kinetic assay">PMID:3743968</ref>. | ||
As an esterase with a catalytically active serine, HGL exhibits an established serine esterase mechanism. The active serine is facilitated first by the neighboring formation of a salt bridge between Asp-136 and His-152, which induces the appropriation of a proton from Ser-153. The now highly nucleophilic Ser-153 will attack the carbonyl carbon of the acetate group in a triacylglycerol molecule. The now tetrahedral species, stabilized by the oxyanion hole; however, as soon as the species disassembles into the covalently bonded acetate and lipase, and the serine undergoes deacylation where water acts at the hydroxyl group. This final step restores Ser-153 to its protonated state<ref name="esterase">PMID:23209280</ref>. | As an esterase with a catalytically active serine, HGL exhibits an established serine esterase mechanism. The active serine is facilitated first by the neighboring formation of a salt bridge between Asp-136 and His-152, which induces the appropriation of a proton from Ser-153. The now highly nucleophilic Ser-153 will attack the carbonyl carbon of the acetate group in a triacylglycerol molecule. The now tetrahedral species, stabilized by the oxyanion hole; however, as soon as the species disassembles into the covalently bonded acetate and lipase, and the serine undergoes deacylation where water acts at the hydroxyl group. This final step restores Ser-153 to its protonated state<ref name="esterase">PMID:23209280</ref>. | ||