Proteopedia - User contributions [en]

User:Allison Welz/Sandbox 1

2021-04-26T21:54:21Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

====Mechanism====
[[Image:mech426.png|200 px|]]
# The triglyceride binds to LPL’s lipid-binding region in an open lid conformation.
# The oxygen on S159 is made more [https://en.wikipedia.org/wiki/Nucleophile nucleophilic]. This happens via [https://en.wikipedia.org/wiki/Histidine histidine] hydrogen bonding with the hydrogen on S159’s alcohol group.
# The nucleophilic oxygen attacks the [https://en.wikipedia.org/wiki/Carbonyl_group carbonyl carbon] of one of the fatty acid chains.
# This pushes electrons up onto the carbonyl oxygen, creating a [http://www.chem.ucla.edu/~harding/IGOC/T/tetrahedral_intermediate.html 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 [https://en.wikipedia.org/wiki/Diglyceride diglyceride] is cleaved.
# H268 hydrogen bonds water, making the oxygen a better nucleophile. Water attacks the carbonyl carbon.
# The [https://en.wikipedia.org/wiki/Carboxylic_acid 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====
<scene name='87/877636/D201_mutation/10'>D201V</scene> is a mutation that is found to cause [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency 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 [https://en.wikipedia.org/wiki/Aspartic_acid carboxyl side chain of aspartate] 201 is one of the coordination sites for the calcium ion of LPL. The mutation to hydrophobic [https://en.wikipedia.org/wiki/Valine valine] means the loss of this coordination site<ref name="Birrane">PMID:30559189</ref>. This mutation adversely affects the folding of LPL and thus affects the secretion of LPL, overall decreasing the activity of LPL<ref name="Birrane">PMID:30559189</ref>.

====M404R====
<scene name='87/877636/M404r_1/2'>M404R</scene> is a mutation found within LPL that caused [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency chylomicronemia] in patients. The hydrophobic [https://en.wikipedia.org/wiki/Methionine methionine] is mutated to the larger and charged side chain of [https://en.wikipedia.org/wiki/Arginine arginine]. Originally it was thought to impact LPL secretion from cells. It was found that the M404R does not affect LPL secretion <ref name="Birrane">PMID:30559189</ref>. 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 <ref name="Birrane">PMID:30559189</ref>.
</StructureSection>

== M404R Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='M404R Mutation w/ GPIHBP-1 Valine Residues' scene='87/877636/M404r_1/1'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

File:Mech426.png

2021-04-26T21:53:26Z

Allison Welz:

File:Lplsimplemech.png

2021-04-26T21:52:15Z

Allison Welz:

User:Allison Welz/Sandbox 1

2021-04-26T21:50:29Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

====Mechanism====
[[Image:mech4.26.png|200 px|]]
# The triglyceride binds to LPL’s lipid-binding region in an open lid conformation.
# The oxygen on S159 is made more [https://en.wikipedia.org/wiki/Nucleophile nucleophilic]. This happens via [https://en.wikipedia.org/wiki/Histidine histidine] hydrogen bonding with the hydrogen on S159’s alcohol group.
# The nucleophilic oxygen attacks the [https://en.wikipedia.org/wiki/Carbonyl_group carbonyl carbon] of one of the fatty acid chains.
# This pushes electrons up onto the carbonyl oxygen, creating a [http://www.chem.ucla.edu/~harding/IGOC/T/tetrahedral_intermediate.html 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 [https://en.wikipedia.org/wiki/Diglyceride diglyceride] is cleaved.
# H268 hydrogen bonds water, making the oxygen a better nucleophile. Water attacks the carbonyl carbon.
# The [https://en.wikipedia.org/wiki/Carboxylic_acid 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====
<scene name='87/877636/D201_mutation/10'>D201V</scene> is a mutation that is found to cause [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency 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 [https://en.wikipedia.org/wiki/Aspartic_acid carboxyl side chain of aspartate] 201 is one of the coordination sites for the calcium ion of LPL. The mutation to hydrophobic [https://en.wikipedia.org/wiki/Valine valine] means the loss of this coordination site<ref name="Birrane">PMID:30559189</ref>. This mutation adversely affects the folding of LPL and thus affects the secretion of LPL, overall decreasing the activity of LPL<ref name="Birrane">PMID:30559189</ref>.

====M404R====
<scene name='87/877636/M404r_1/2'>M404R</scene> is a mutation found within LPL that caused [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency chylomicronemia] in patients. The hydrophobic [https://en.wikipedia.org/wiki/Methionine methionine] is mutated to the larger and charged side chain of [https://en.wikipedia.org/wiki/Arginine arginine]. Originally it was thought to impact LPL secretion from cells. It was found that the M404R does not affect LPL secretion <ref name="Birrane">PMID:30559189</ref>. 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 <ref name="Birrane">PMID:30559189</ref>.
</StructureSection>

== M404R Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='M404R Mutation w/ GPIHBP-1 Valine Residues' scene='87/877636/M404r_1/1'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-04-26T21:18:52Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

====Mechanism====
[[Image:MechFinalAllison.png|200 px|]]
# The triglyceride binds to LPL’s lipid-binding region in an open lid conformation.
# The oxygen on S159 is made more [https://en.wikipedia.org/wiki/Nucleophile nucleophilic]. This happens via [https://en.wikipedia.org/wiki/Histidine histidine] hydrogen bonding with the hydrogen on S159’s alcohol group.
# The nucleophilic oxygen attacks the [https://en.wikipedia.org/wiki/Carbonyl_group carbonyl carbon] of one of the fatty acid chains.
# This pushes electrons up onto the carbonyl oxygen, creating a [http://www.chem.ucla.edu/~harding/IGOC/T/tetrahedral_intermediate.html 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 [https://en.wikipedia.org/wiki/Diglyceride diglyceride] is cleaved.
# H268 hydrogen bonds water, making the oxygen a better nucleophile. Water attacks the carbonyl carbon.
# The [https://en.wikipedia.org/wiki/Carboxylic_acid 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====
<scene name='87/877636/D201_mutation/10'>D201V</scene> is a mutation that is found to cause [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency 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 [https://en.wikipedia.org/wiki/Aspartic_acid carboxyl side chain of aspartate] 201 is one of the coordination sites for the calcium ion of LPL. The mutation to hydrophobic [https://en.wikipedia.org/wiki/Valine valine] means the loss of this coordination site<ref name="Birrane">PMID:30559189</ref>. This mutation adversely affects the folding of LPL and thus affects the secretion of LPL, overall decreasing the activity of LPL<ref name="Birrane">PMID:30559189</ref>.

====M404R====
<scene name='87/877636/M404r_1/2'>M404R</scene> is a mutation found within LPL that caused [https://en.wikipedia.org/wiki/Lipoprotein_lipase_deficiency chylomicronemia] in patients. The hydrophobic [https://en.wikipedia.org/wiki/Methionine methionine] is mutated to the larger and charged side chain of [https://en.wikipedia.org/wiki/Arginine arginine]. Originally it was thought to impact LPL secretion from cells. It was found that the M404R does not affect LPL secretion <ref name="Birrane">PMID:30559189</ref>. 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 <ref name="Birrane">PMID:30559189</ref>.
</StructureSection>

== M404R Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='M404R Mutation w/ GPIHBP-1 Valine Residues' scene='87/877636/M404r_1/1'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-04-26T21:08:37Z

Allison Welz:

User:Allison Welz/Sandbox 1

2021-03-30T19:37:24Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

=== Mechanism ===

== Disease ==

=== Mutations ===
== D201V Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='D201 Mutation with Calcium Ion' scene='87/877636/D201_mutation/7'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== M404R Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='M404R Mutation w/ GPIHBP-1 Valine Residues' scene='87/877636/M404r_1/1'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-03-23T20:13:33Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

=== Mechanism ===

== Disease ==

=== Mutations ===
== D201V Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='D201 Mutation with Calcium Ion' scene='87/877636/D201_mutation/7'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-03-23T20:08:28Z

Allison Welz: D201V Mutation

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>

== Introduction ==

=== History ===

=== Significance ===

== Function ==

=== Mechanism ===

== Disease ==

=== Mutations ===
== D201V Mutation ==
<StructureSection load='3rec' size='350' side='right' caption='D201 Mutation with Calcium Ion' scene='D201_Mutation'>

Anything in this section will appear adjacent to the 3D structure and will be scrollable.

</StructureSection>

== Relevance ==

== Structural highlights ==

</StructureSection>

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

File:2021-03-16.png

2021-03-16T19:41:09Z

Allison Welz:

File:Inhibitor and catalytic triad.pse

2021-03-16T19:35:52Z

Allison Welz:

User:Allison Welz/Sandbox 1

2021-03-16T19:34:00Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Allison Welz/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.
== Introduction ==

=== History ===

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

== Student Contributors ==

*Ashrey Burley
*Allison Welz
*Hannah Wright

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-03-16T19:23:14Z

Allison Welz:

=LPL with GPIHBP-1,'' Drosophilia S2''=
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Allison Welz/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz/Sandbox 1

2021-03-16T19:17:26Z

Allison Welz: New page: ==Your Heading Here (maybe something like 'Structure')== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for you...

==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Allison Welz/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

== Function ==

== Disease ==

== Relevance ==

== Structural highlights ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

User:Allison Welz

2021-03-16T19:15:00Z

Allison Welz:

* Full Real Name: Allison Welz

* Position: Student

* Institution (NO ABBREVIATIONS): Butler University

* City, State/Province, Country: Indianapolis, Indiana, the United States of America

* Field of Expertise or Study:
[[User:Allison Welz/Sandbox 1]]