Sandbox 49

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==Introduction==
==Introduction==
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Lipases represent a critical class of enzymes that functions in the breakdown of triacylglycerides. Produced by the pancreas, lipase catalyzes the hydrolysis of triacylglyercols at their 1 and 3 carbons, resulting the in the production of 2-monoacylglycerols and free fatty acids. Modeled here is horse pancreatic lipase. The structure of
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Lipases represent a critical class of enzymes that functions in the breakdown of triacylglycerides. Produced by the pancreas, lipase catalyzes the hydrolysis of triacylglyercols at their 1 and 3 carbons, resulting the in the production of 2-monoacylglycerols and free fatty acids. Modeled here is horse pancreatic lipase.
==Structure==
==Structure==

Revision as of 16:30, 15 March 2012

Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013.

PDB ID 1hpl

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Contents

Introduction

Lipases represent a critical class of enzymes that functions in the breakdown of triacylglycerides. Produced by the pancreas, lipase catalyzes the hydrolysis of triacylglyercols at their 1 and 3 carbons, resulting the in the production of 2-monoacylglycerols and free fatty acids. Modeled here is horse pancreatic lipase.

Structure

Lipase has 449 amino acid resiudes, and 2 domains, the is smaller with 112 residues, and the consists of 337 residues. Notice that each of these domains consist of 2 identical subunits. Lipase has an a chain and a b chain that each respectively contain 1 of the subunits of the C Terminal Domain and 1 of the subunits of the N terminal domains, all 4 parts come together to form the fully functional enzyme.

The secondary structural elements of Lipase, including the that make up 30 percent of the amino acid chain, and involving 139 residues as well as the that make up 22 percent and 102 residues characterize the structure of the protein.

Important for the tertiary structure of the protein, are several different factors that function to hold each of the domains together in the proper orientation, the certainly make a difference as one might expect, since all proteins generally fold to shield these from interaction with water, the cysteine residues that Lipase has also play a major role since they form , Lipase has 12 disulfide bonds in all.

Lipase Active Sites

The Lipase Active Sites consists of a catalytic triad of residues: Ser 152, Asp 176, and His 263. Residues Phe 77 and Leu 153 are also important for the mechanism of Lipase. The catalytic triad is covered by a “lid” that protects the active site of the enyzyme, and prevents the binding of substrate when it is closed and covering the active site. In total lipase has 2 active sites, 1 for each of the domains that make up the enzyme.

Mechanism

The mechanism of action for pancreatic lipase can be broken down into 4 main steps. In the first step His 263 deprotonates Ser 152 that in turn attacks the carboxy carbon of triacylglyceride substrate, it is a nucleophilic addition reaction. In the second step of the reaction the oxyanion hole collapses resulting in the elimination of the diacylglycerol product, that deprotonates His 263 and acylates Ser 152 as a result. In the third step His 263 deprotonates water, which in turn attacks the carboxyl carbon of the acylated Ser 152 in another nucleophilic addition reaction. And in the last step the oxyanion hole collapses again resulting in the elimination of the carboxylate product and Ser 152 which then deprotonates His 263. The reaction of pancreatic lipase is displayed in the following figures.

Reaction 1: Image:M0218.stg01.gif

Reaction 2: Image:M0218.stg02.gif

Reaction 3: Image:M0218.stg03.gif

Reaction 4: Image:M0218.stg04.gif

Ca Ligand

Lipase also has a Ca Ligand that noncovalently binds to residues: Glu 187, Arg 190, Asp 192, Asp 195. There is one Calcium ion bound per chain in the enzyme, so that makes a total of 2 calcium ligands per enzyme. The Ca ligand is an important factor involved in the activation of the enzyme.

Inhibition and Activation

References


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