User:Maggie Stopa/Sandbox 1
From Proteopedia
< User:Maggie Stopa(Difference between revisions)
| (3 intermediate revisions not shown.) | |||
| Line 5: | Line 5: | ||
It should be noted that the PDB: 6OB0 was used to synthesize the following images. | It should be noted that the PDB: 6OB0 was used to synthesize the following images. | ||
| - | <scene name='87/877513/Original_scene/1'>Lipoprotein Lipase</scene>(LPL) is an important enzyme for the breakdown of triglycerides in the body (Figure 1).<ref name=”Arora”>PMID:31072929</ref> [[Image:Simple_mech.png|400 px|right|thumb|Figure 1: breakdown of a triglyceride into a diglyceride and creation of one free fatty acid by LPL]] A [http://en.wikipedia.org/wiki/Lipase lipase] is an enzyme that is capable of catalyzing the [http://en.wikipedia.org/wiki/Hydrolysis hydrolysis] of fats/lipids which are consumed through oils. It is encoded by the [http://www.genecards.org/cgi-bin/carddisp.pl?gene=LPL p22 region in chromosome 8]. Once synthesized, it is secreted into the interstitial space in several tissues. The main site of action for <scene name='87/877513/Original_scene/1'>LPL</scene> is in the [http://www.pnas.org/content/pnas/116/5/1480/F1.large.jpg capillary lumen] within muscle and adipose tissues.<ref name=”Birrane”>PMID:30559189</ref> The function of this lipase is to hydrolyze [http://en.wikipedia.org/wiki/Triglyceride triglycerides] of very-low-density lipoproteins ([http://qph.fs.quoracdn.net/main-qimg-8e874e647baeb69b00203c47165247e2 VLDL]) and to aid in the delivery of lipid nutrients to vital tissues.<ref name=”Birrane”>PMID:30559189</ref> The enzyme is commonly found on the surface of cells that line blood capillaries. Two different lipoproteins are essential to break down triglycerides. One of | + | <scene name='87/877513/Original_scene/1'>Lipoprotein Lipase</scene>(LPL) is an important enzyme for the breakdown of triglycerides in the body (Figure 1).<ref name=”Arora”>PMID:31072929</ref> [[Image:Simple_mech.png|400 px|right|thumb|Figure 1: breakdown of a triglyceride into a diglyceride and creation of one free fatty acid by LPL]] A [http://en.wikipedia.org/wiki/Lipase lipase] is an enzyme that is capable of catalyzing the [http://en.wikipedia.org/wiki/Hydrolysis hydrolysis] of fats/lipids which are consumed through oils. It is encoded by the [http://www.genecards.org/cgi-bin/carddisp.pl?gene=LPL p22 region in chromosome 8]. Once synthesized, it is secreted into the interstitial space in several tissues. The main site of action for <scene name='87/877513/Original_scene/1'>LPL</scene> is in the [http://www.pnas.org/content/pnas/116/5/1480/F1.large.jpg capillary lumen] within muscle and adipose tissues.<ref name=”Birrane”>PMID:30559189</ref> The function of this lipase is to hydrolyze [http://en.wikipedia.org/wiki/Triglyceride triglycerides] of very-low-density lipoproteins ([http://qph.fs.quoracdn.net/main-qimg-8e874e647baeb69b00203c47165247e2 VLDL]) and to aid in the delivery of lipid nutrients to vital tissues.<ref name=”Birrane”>PMID:30559189</ref> The enzyme is commonly found on the surface of cells that line blood capillaries. Two different lipoproteins are essential to break down triglycerides. One of them is utilized to transport fat into the bloodstream from different organs.<ref name=”Arora”>PMID:31072929</ref> A type of these lipoproteins, called [http://en.wikipedia.org/wiki/Chylomicron chylomicrons] are essential in the transport of long chain triglyceride from the small intestine to the tissues. The hydrolysis of triglycerides by lipoprotein lipase results in fat molecules being used by the body as energy or for storage in fatty tissue. <ref name=”Arora”>PMID:31072929</ref><ref name=”Mead”>PMID:12483461</ref> |
==Structural Overview== | ==Structural Overview== | ||
| Line 20: | Line 20: | ||
=== Lid and Lipid Binding Region === | === Lid and Lipid Binding Region === | ||
| - | In the presence of the GPIHBP1 inhibitor, the <scene name='87/877513/Lid_region_final/2'>lid region</scene> and <scene name='87/877513/Inhibitorsbound/ | + | In the presence of the GPIHBP1 inhibitor, the <scene name='87/877513/Lid_region_final/2'>lid region</scene> and <scene name='87/877513/Inhibitorsbound/4'>lipid-binding region</scene> become visible within the structure. As displayed through a study conducted by Arora et. al, in 2019, the lipid-binding region of LPL actively interacts with the known inhibitor in the heterodimeric form. <ref name=”Arora”>PMID:31072929</ref> This was established to be the only time that the heterodimeric form was shown as an active lipase. The lid region residues Ile245, Ile249, V251, Ile252, Leu257, Val260, Leu263, and Val264, are found as an open conformation which is composed of two small alpha helices that reach out and away from the protein. The lid and lipid-binding region create hydrophobic patches on the surface of lipoprotein lipase which are essential for <scene name='87/877513/Lipid_binding_and_lid/1'>ligand binding</scene> by LPL. |
| - | + | ||
==Mechanism== | ==Mechanism== | ||
Lipoprotein Lipase functions to catalyze the hydrolysis of one [http://en.wikipedia.org/wiki/Ester ester bond] of triglycerides in order to remove one fatty acid tail and turn the triglyceride into a diglyceride. It does this by utilizing a simple [http://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolase] mechanism, in which it uses a <scene name='87/877513/Catalytic_triad-1/6'>catalytic triad</scene> composed of Asp183, His268, and Ser159 to catalyze the hydrolysis. His268 serves as a base catalyst by deprotonation of Ser159, which can then serve as the [http://en.wikipedia.org/wiki/Nucleophile nucleophile] to attack the carbonyl carbon of one of the fatty acid chains of a triglyceride. This forms a tetrahedral intermediate, which is stabilized by the amide of Trp82 and Leu160 residues, called the <scene name='87/877513/Oxyanion_hole_-_labeled/9'>oxyanion hole</scene>. The single fatty acid chain is cleaved from the triglyceride, forming the diglyceride product. Then, water is used to free the fatty acid from Ser159 and return all of the residues back to their starting point, in order to perform the mechanism again on another triglyceride. Ultimately, the hydrolysis results in the formation of one free fatty acid and glycerol with two fatty acid tails (Figure 2). | Lipoprotein Lipase functions to catalyze the hydrolysis of one [http://en.wikipedia.org/wiki/Ester ester bond] of triglycerides in order to remove one fatty acid tail and turn the triglyceride into a diglyceride. It does this by utilizing a simple [http://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolase] mechanism, in which it uses a <scene name='87/877513/Catalytic_triad-1/6'>catalytic triad</scene> composed of Asp183, His268, and Ser159 to catalyze the hydrolysis. His268 serves as a base catalyst by deprotonation of Ser159, which can then serve as the [http://en.wikipedia.org/wiki/Nucleophile nucleophile] to attack the carbonyl carbon of one of the fatty acid chains of a triglyceride. This forms a tetrahedral intermediate, which is stabilized by the amide of Trp82 and Leu160 residues, called the <scene name='87/877513/Oxyanion_hole_-_labeled/9'>oxyanion hole</scene>. The single fatty acid chain is cleaved from the triglyceride, forming the diglyceride product. Then, water is used to free the fatty acid from Ser159 and return all of the residues back to their starting point, in order to perform the mechanism again on another triglyceride. Ultimately, the hydrolysis results in the formation of one free fatty acid and glycerol with two fatty acid tails (Figure 2). | ||
| Line 37: | Line 37: | ||
== References == | == References == | ||
| + | |||
<references/> | <references/> | ||
Current revision
Lipoprotein Lipase coupled with GPIHBP1
| |||||||||||
