Sandbox 43: Difference between revisions

Line 21:

[[Image:Hydrolysis.gif|200px|right|thumb| Lipase-catalyzed hydrolysis of lipids. Notice the catalytic triad of Ser-152, Asp-176, and His-263 that constitute the active site.<ref>http://www.pnas.org/content/101/16/5716.full</ref>]]

After colipase binds to the C-terminus and the structural modifications of lipase take place (opening the "lipase lid"), the active site is exposed and the lipid binds, initiating its catalysis. <scene name='Sandbox_43/Asp_176/1'>Asp-176</scene> acts as a base and removes the proton from <scene name='Sandbox_43/Ser_152/3'>His-263</scene>. This allows His-263 to push electrons towards <scene name='Sandbox_43/Ser_152/2'>Ser-152</scene>, removing the hydrogen from serine's alcohol. Consequently, the nucleophilicity of the now-charged oxygen atom on Ser-152 is greatly increased, promoting its attack of one of the ester carbons of the triglyceride. Through the nucleophilic acyl substitution mechanism, Ser-152 forms a tertrahedral intermediate with the lipid, which consequently exposes the former carbonyl oxygen (now negatively charged) to the oxyanion hole. Coming out of this stabilized transition state, the first product of the reaction (an alcohol) is pushed off the carbonyl carbon as the ester is reformed. Finally, hydrolysis can take place and the second product, the free fatty acid, leaves and the alcohol substituent of Ser-152 is reformed.<ref>http://www.pnas.org/content/101/16/5716.full</ref>

After colipase binds to the C-terminus and the structural modifications of lipase take place (opening the "lipase lid"), the active site is exposed and the lipid binds, initiating its catalysis. <scene name='Sandbox_43/Asp_176/1'>Asp-176</scene> acts as a base and removes the proton from <scene name='Sandbox_43/Ser_152/3'>His-263</scene>. This allows His-263 to push electrons towards <scene name='Sandbox_43/Ser_152/2'>Ser-152</scene>, removing the hydrogen from serine's alcohol. Consequently, the nucleophilicity of the now-charged oxygen atom on Ser-152 is greatly increased, promoting its attack of one of the ester carbons of the triglyceride. Through the nucleophilic acyl substitution mechanism, Ser-152 forms a tertrahedral intermediate with the lipid, which consequently exposes the former carbonyl oxygen (now negatively charged) to the <scene name='Sandbox_45/Oxyhole/2'>oxyanion hole</scene>. Coming out of this stabilized transition state, the first product of the reaction (an alcohol) is pushed off the carbonyl carbon as the ester is reformed. Finally, hydrolysis can take place and the second product, the free fatty acid, leaves and the alcohol substituent of Ser-152 is reformed.<ref>http://www.pnas.org/content/101/16/5716.full</ref>

Sandbox 43: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

Revision as of 02:29, 14 November 2011 view source Student (talk \| contribs) students 33,923 edits No edit summary ← Older edit		Revision as of 02:43, 14 November 2011 view source Student (talk \| contribs) students 33,923 edits No edit summary Newer edit →
Line 21:		Line 21:
	[[Image:Hydrolysis.gif\|200px\|right\|thumb\| Lipase-catalyzed hydrolysis of lipids. Notice the catalytic triad of Ser-152, Asp-176, and His-263 that constitute the active site.<ref>http://www.pnas.org/content/101/16/5716.full</ref>]]		[[Image:Hydrolysis.gif\|200px\|right\|thumb\| Lipase-catalyzed hydrolysis of lipids. Notice the catalytic triad of Ser-152, Asp-176, and His-263 that constitute the active site.<ref>http://www.pnas.org/content/101/16/5716.full</ref>]]

	After colipase binds to the C-terminus and the structural modifications of lipase take place (opening the "lipase lid"), the active site is exposed and the lipid binds, initiating its catalysis. <scene name='Sandbox_43/Asp_176/1'>Asp-176</scene> acts as a base and removes the proton from <scene name='Sandbox_43/Ser_152/3'>His-263</scene>. This allows His-263 to push electrons towards <scene name='Sandbox_43/Ser_152/2'>Ser-152</scene>, removing the hydrogen from serine's alcohol. Consequently, the nucleophilicity of the now-charged oxygen atom on Ser-152 is greatly increased, promoting its attack of one of the ester carbons of the triglyceride. Through the nucleophilic acyl substitution mechanism, Ser-152 forms a tertrahedral intermediate with the lipid, which consequently exposes the former carbonyl oxygen (now negatively charged) to the oxyanion hole. Coming out of this stabilized transition state, the first product of the reaction (an alcohol) is pushed off the carbonyl carbon as the ester is reformed. Finally, hydrolysis can take place and the second product, the free fatty acid, leaves and the alcohol substituent of Ser-152 is reformed.<ref>http://www.pnas.org/content/101/16/5716.full</ref>		After colipase binds to the C-terminus and the structural modifications of lipase take place (opening the "lipase lid"), the active site is exposed and the lipid binds, initiating its catalysis. <scene name='Sandbox_43/Asp_176/1'>Asp-176</scene> acts as a base and removes the proton from <scene name='Sandbox_43/Ser_152/3'>His-263</scene>. This allows His-263 to push electrons towards <scene name='Sandbox_43/Ser_152/2'>Ser-152</scene>, removing the hydrogen from serine's alcohol. Consequently, the nucleophilicity of the now-charged oxygen atom on Ser-152 is greatly increased, promoting its attack of one of the ester carbons of the triglyceride. Through the nucleophilic acyl substitution mechanism, Ser-152 forms a tertrahedral intermediate with the lipid, which consequently exposes the former carbonyl oxygen (now negatively charged) to the <scene name='Sandbox_45/Oxyhole/2'>oxyanion hole</scene>. Coming out of this stabilized transition state, the first product of the reaction (an alcohol) is pushed off the carbonyl carbon as the ester is reformed. Finally, hydrolysis can take place and the second product, the free fatty acid, leaves and the alcohol substituent of Ser-152 is reformed.<ref>http://www.pnas.org/content/101/16/5716.full</ref>