User:Allison Welz/Sandbox 1

LPL with GPIHBP-1, Drosophilia S2

spinqualitylabelsall models Caption for this structure Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Function Mechanism The triglyceride binds to LPL’s lipid-binding region in an open lid conformation. The oxygen on S159 is made more nucleophilic. This happens via histidine hydrogen bonding with the hydrogen on S159’s alcohol group. The nucleophilic oxygen attacks the carbonyl carbon of one of the fatty acid chains. This pushes electrons up onto the carbonyl oxygen, creating a tetrahedral intermediate. This is the oxyanion hole which is stabilized by main chain nitrogen atoms of W82 and L160. One of the lone pairs of the oxygen (in the oxyanion hole) creates a double bond carbon. The oxygen-carbon bond between the single fatty acid chain and the diglyceride is cleaved. H268 hydrogen bonds water, making the oxygen a better nucleophile. Water attacks the carbonyl carbon. The carboxylic acid is formed and the S159 bond is cleaved and re-protonated via H268. The active site is now back in its original state. Disease Mutations D201V D201V is a mutation that is found to cause chylomicronemia. Chylomicronemia is when the body cannot break down lipids properly. This leads to their build-up in the body causing high levels of triglycerides in the body. The carboxyl side chain of aspartate 201 is one of the coordination sites for the calcium ion of LPL. The mutation to hydrophobic valine means the loss of this coordination site. This mutation adversely affects the folding of LPL and thus affects the secretion of LPL, overall decreasing the activity of LPL. M404R M404R is a mutation found within LPL that caused chylomicronemia in patients. The hydrophobic methionine is mutated to the larger and charged side chain of arginine. Originally it was thought to impact LPL secretion from cells. It was found that the M404R does not affect LPL secretion . M404R interacts with the hydrophobic pocket of GPIHBP1’s finger 3 of its 3 fingered domain (V121, E122, T124, V126). The large, charged arginine repelled the hydrophobic pocket and does not fit well. This prevents proper binding and formation of the LPL-GPIHBP1 complex .

M404R Mutation

spinqualitylabelsall models M404R Mutation w/ GPIHBP-1 Valine Residues Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Anything in this section will appear adjacent to the 3D structure and will be scrollable.

Structural highlights

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Student Contributors

• Ashrey Burley
• Allison Welz
• Hannah Wright

This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

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Proteopedia Page Contributors and Editors (what is this?)

Allison Welz