Sandbox Reserved 1675
From Proteopedia
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| - | == | + | ==Human PYCR-1 Complexed with NFLP== |
| - | <StructureSection load=' | + | <StructureSection load='6XP0' size='340' side='right' caption='Caption for this structure' scene=''> |
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| - | == Function == | + | == Function of your protein == |
| + | Converts P5C to proline. When complexed with NFLP, NFLP inhibits this function, interrupting the proline cycle in cancerous cells, and decreasing spheroid growth. <ref>PMID:33109600</ref> | ||
| - | == | + | == Biological relevance and broader implications == |
| + | PYCR-1 has been shown to have have many effects on the survival and proliferation of cancerous cells when the proline cycle is able to continue <ref>PMID:33109600</ref>. NFLP is a competitive inhibitor of PYCR-1. When NFLP is able to bind it changes the conformation of the protein, which in turn makes it unable to convert P5C to proline, and disrupts the proline cycle <ref>PMID:33109600</ref>. In this way, NFLP shows potential for further research into reducing the success of cancerous cells. Since NFLP is a competitive inhibitor, this means that some PYCR-1 protein will still bind P5C and partake in the proline cycle. NFLP then shows promise to reduce, but not eliminate the proliferation of cancer. Research should be done into any analogs of NFLP which could prove to be more successful inhibitors. | ||
| - | == | + | == Important amino acids== |
| + | When we look at the primary structure of the protein, there are specific amino acids important to the binding on NFLP. These amino acids are Histidine 223, Aspartic acid 229, Valine 231, Serine 233, and Alanine 237<ref>PMID:33109600</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
| + | <scene name='87/873237/Ligand_view/2'>This view of the protein shows the ligand, and it's primary interactions with amino acids of alpha helixes in the internal structure of the protein. The internal alpha helices are where the catalytic triad is found. </scene> <scene name='87/873237/Secondary_structure/2'>This view of the protein shows that the secondary structures consists of roughly 80% alpha helixes, 15% beta sheets, and 5% other structures.</scene> | ||
| - | + | <scene name='87/873237/Active_site_fixed/5'>NFLP binding with Val 231, and interaction between His 223 and Asp 229 shown in stick and wire.</scene> | |
| + | <scene name='87/873237/Active_site_fixed/6'>Shown in stick and wire, with non binding amino acids in cartoon for representation.</scene> <scene name='87/873237/Active_site_fixed/7'>Shown in space filing for representation.</scene> | ||
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| + | == Other important features == | ||
| + | <scene name='87/873237/Proline_bound/1'>PYCR-1 bound to proline for cross reference, in stick and wire,</scene> <scene name='87/873237/Proline_bound/2'>ribbon,</scene> <scene name='87/873237/Proline_bound/3'>and space fill. | ||
| + | </scene> | ||
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| + | The other unique feature that allows NFLP to bind more tightly than proline is that the alphaK helices rotate 1 angstrom, <scene name='87/873237/Proline_bound_his/2'>which causes his-223 on each subunit to avoid a steric clash</scene>, and the helices glide past each other, which makes the molecule more capable of accommodating the formyl group of NFLP<ref>PMID:33109600</ref>. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
| This Sandbox is Reserved from 01/25/2021 through 04/30/2021 for use in Biochemistry taught by Bonnie Hall at Grand View University, Des Moines, USA. This reservation includes Sandbox Reserved 1665 through Sandbox Reserved 1682. |
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Human PYCR-1 Complexed with NFLP
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References
- ↑ Christensen EM, Bogner AN, Vandekeere A, Tam GS, Patel SM, Becker DF, Fendt SM, Tanner JJ. In Crystallo Screening for Proline Analog Inhibitors of the Proline Cycle Enzyme PYCR1. J Biol Chem. 2020 Oct 27. pii: RA120.016106. doi: 10.1074/jbc.RA120.016106. PMID:33109600 doi:http://dx.doi.org/10.1074/jbc.RA120.016106
- ↑ Christensen EM, Bogner AN, Vandekeere A, Tam GS, Patel SM, Becker DF, Fendt SM, Tanner JJ. In Crystallo Screening for Proline Analog Inhibitors of the Proline Cycle Enzyme PYCR1. J Biol Chem. 2020 Oct 27. pii: RA120.016106. doi: 10.1074/jbc.RA120.016106. PMID:33109600 doi:http://dx.doi.org/10.1074/jbc.RA120.016106
- ↑ Christensen EM, Bogner AN, Vandekeere A, Tam GS, Patel SM, Becker DF, Fendt SM, Tanner JJ. In Crystallo Screening for Proline Analog Inhibitors of the Proline Cycle Enzyme PYCR1. J Biol Chem. 2020 Oct 27. pii: RA120.016106. doi: 10.1074/jbc.RA120.016106. PMID:33109600 doi:http://dx.doi.org/10.1074/jbc.RA120.016106
- ↑ Christensen EM, Bogner AN, Vandekeere A, Tam GS, Patel SM, Becker DF, Fendt SM, Tanner JJ. In Crystallo Screening for Proline Analog Inhibitors of the Proline Cycle Enzyme PYCR1. J Biol Chem. 2020 Oct 27. pii: RA120.016106. doi: 10.1074/jbc.RA120.016106. PMID:33109600 doi:http://dx.doi.org/10.1074/jbc.RA120.016106
- ↑ Christensen EM, Bogner AN, Vandekeere A, Tam GS, Patel SM, Becker DF, Fendt SM, Tanner JJ. In Crystallo Screening for Proline Analog Inhibitors of the Proline Cycle Enzyme PYCR1. J Biol Chem. 2020 Oct 27. pii: RA120.016106. doi: 10.1074/jbc.RA120.016106. PMID:33109600 doi:http://dx.doi.org/10.1074/jbc.RA120.016106
