Proteopedia - User contributions [en]

File:MTHFR Reaction.jpg

2022-05-04T18:58:38Z

Shaylie Albright: uploaded a new version of "Image:MTHFR Reaction.jpg": Updated version to highlight the electrons associated with the hydride transfer

== Summary ==
The reduction of 5,10 MTHF to 5 MTHF catalyzed by the enzyme MTHFR
== Licensing ==
{{self|cc-by-sa-3.0|GFDL}}

Methylenetetrahydrofolate reductase

2022-05-04T18:48:02Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs<ref>https://doi.org/10.1038/s41467-018-04735-2</ref>.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties. Additionally, FADH2 is the prosthetic group which acts as an oxidizing or reducing agent depending on the oxidation state of the substrates NADH or 5,10MTHF. When 5,10 MTHF binds FADH2 acts as a reducing agent, and when NADH binds FADH2 is reduced back to its inital state to allow the cycle to continue.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders<ref>Leclerc D, Sibani S, Rozen R. Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6561/</ref>.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a <scene name='90/907473/Mthfr_protein/3'>dimer</scene>. The <scene name='90/907473/Mthfr_protein/4'>N- and C-terminal domains of MTHFR</scene> are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/7'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
==Acknowledgements==
I would like to thank Dr. Karsten Theis for his support and aid in the construction of this page. I would also like to thank Dr. Kristen Procko for her review and critiques. Lastly, I thank my classmates Michael O'Shaughnessy, Kia Yang, and Anna Postnikova for their thoughts and contributions on this project.

== References ==
<references/>
[[Category:One-carbon metabolism]]
[[Category:5-methyltetrahydrofolate]]

Methylenetetrahydrofolate reductase

2022-05-04T18:41:50Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs<ref>https://doi.org/10.1038/s41467-018-04735-2</ref>.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders<ref>Leclerc D, Sibani S, Rozen R. Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6561/</ref>.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a <scene name='90/907473/Mthfr_protein/3'>dimer</scene>. The <scene name='90/907473/Mthfr_protein/4'>N- and C-terminal domains of MTHFR</scene> are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/7'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
==Acknowledgements==
I would like to thank Dr. Karsten Theis for his support and aid in the construction of this page. I would also like to thank Dr. Kristen Procko for her review and critiques. Lastly, I thank my classmates Michael O'Shaughnessy, Kia Yang, and Anna Postnikova for their thoughts and contributions on this project.

== References ==
<references/>
[[Category:One-carbon metabolism]]
[[Category:5-methyltetrahydrofolate]]

Methylenetetrahydrofolate reductase

2022-04-27T14:57:46Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs<ref>https://doi.org/10.1038/s41467-018-04735-2</ref>.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders<ref>Leclerc D, Sibani S, Rozen R. Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6561/</ref>.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a <scene name='90/907473/Mthfr_protein/3'>dimer</scene>. The <scene name='90/907473/Mthfr_protein/4'>N- and C-terminal domains of MTHFR</scene> are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/7'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-27T14:56:13Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders<ref>Leclerc D, Sibani S, Rozen R. Molecular biology of methylenetetrahydrofolate reductase (MTHFR) and overview of mutations/polymorphisms. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK6561/</ref>.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a <scene name='90/907473/Mthfr_protein/3'>dimer</scene>. The <scene name='90/907473/Mthfr_protein/4'>N- and C-terminal domains of MTHFR</scene> are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/7'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-25T14:56:54Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a dimer(<scene name='90/907473/Mthfr_protein/2'>reload initial scene</scene>). The N- and C-terminal domains of MTHFR are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/6'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-25T14:56:32Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a dimer(<scene name='90/907473/Mthfr_protein/2'>reload initial scene</scene>). The N- and C-terminal domains of MTHFR are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/6'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-25T14:55:52Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+
[[Image:MTHFR Reaction.jpg|800px]]

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a dimer(<scene name='90/907473/Mthfr_protein/2'>reload initial scene</scene>). The N- and C-terminal domains of MTHFR are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/6'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-25T14:52:11Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a dimer(<scene name='90/907473/Mthfr_protein/2'>reload initial scene</scene>). The N- and C-terminal domains of MTHFR are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/6'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-25T14:33:18Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme that is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

5,10-methylenetetrahydrofolate + NADPH + H+ → 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

==Mechanism==
This reaction mechanism is characterized by a hydride transfer (highlighted in yellow) from the FADH to the partially positive 5,10-methyl group. This causes the 5-membered ring to open and Nitrogen 10 to receive the electrons that were involved in the C-N10 bond. This allows Nitrogen 10 to act as a Bronsted-Lowry base and accept the proton highlighted in green.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Structure ==
<StructureSection load='' size='400' side='right' scene='90/907473/Mthfr_protein/2'>
MTHFR occurs as a dimer(<scene name='90/907473/Mthfr_protein/2'>reload initial scene</scene>). The N- and C-terminal domains of MTHFR are joined together by a linker (red). The N-terminal domain (silver) functions as the catalytic domain to convert 5,10-MTHF to 5-MTHF (this product will be used with [[Methionine synthase]]). This domain contains FAD as a cofactor and binds to NADPH as an electron donor<ref>PMID:16114881</ref>. The C-terminal (yellow) functions as the regulatory domain and binds to SAH, to recognize the need for inhibition or activation.

MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/6'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.
{{Template:Button Toggle Animation2}}<jmol>
<jmolCheckbox>
<scriptWhenUnChecked>select NAI or C2F or FAD; spacefill off;
</scriptWhenUnChecked>
<scriptWhenchecked>select NAI or C2F or FAD; spacefill on;
</scriptWhenchecked>
<checked>false</checked>
<text>Ligands as spacefilling</text>
</jmolCheckbox>
</jmol>

[[Image:MTHFR ping pong.gif]]

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Thymidylate synthase

2022-04-20T15:22:28Z

Shaylie Albright:

Thymidylate Synthase (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>

2-deoxyuridine-5'-monophosphate(dUMP) + 5, 10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F)

[[Image:TS Overview.jpg]]
== Function ==
'''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair<ref>PMID:2243092</ref>. In protozoa, [[dihydrofolate reductase]] (DHFR) and TS are expressed as a bifunctional monomeric enzyme ('''DHFR-TS)''' with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – '''ThyA''' and '''ThyX'''. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.

== Relevance ==
One of the nucleobase of DNA, cytosine, spontaneously deaminates to form uracil, changing the encoded message. Different from RNA, DNA does not contain uracil but instead contains the methylated form thymine, avoiding missense mutations. The [https://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair protein] [[Uracil DNA glycosylase]] will recognize uracil as damaged DNA, removing it and re-establishing the original message<ref>DOI:10.1038/sj.onc.1205996</ref>. Because thymine contains an additional methyl group, it is distinguishable from uracil, and is not removed through DNA repair. Thymidylate synthase helps to turn the abundant uridine (containing the nucleobase uracil) into deoxythymidine (containing the nucleobase thymine) in preparation for DNA synthesis prior to cell division. Thus, thymidylate synthase plays a role in making DNA a more reliable long-term storage of genetic information compared to RNA.

TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>

<StructureSection load='' size='350' side='right' caption='Thymidylate synthase complex with dUMP (PDB entry [[1tsv]])' scene='49/493689/Cv/1'>
==Structure and ligand binding==
TS forms a homodimer consisting of two domains (reload <scene name='49/493689/Cv/1'>initial scene</scene>). Their <scene name='49/493689/Cv/4'>active sites can each bind the substrate dUMP</scene><ref>PMID:9053905</ref>. Maley et al. show that E.coli TS uses a half-the-sites mechanism when catalyzing its reaction<ref>DOI:10.1021/bi00005a001</ref>. One of the two active sites catalyzes the reaction while the other remains inactive. The way the two domains communicate with each other to coordinate this is still unknown.

The active site Cysteine has two <scene name='49/493689/Ts_7jxf_percentb/4'>conformations</scene>. Conformation 1 shows the active site cysteine unbound to the intermediate 4.21 Angstroms away from the C6 carbon of the dNMP ring. Conformation 2 shows the active site cysteine bound to the intermediate 3.84 Angstroms away from the C6 carbon of the dNMP ring.
<jmol>
<jmolRadioGroup>
<item>
<script>hide (VNM or 146:B) and altloc=A</script>
<text>Conformation 1</text>
<checked>true</checked>
</item>
<item>
<script>hide (VNM or 146:B) and altloc=B</script>
<text>Conformation 2</text>
<checked>false</checked>
</item>
<item>
<script>hide none</script>
<text>both conformations</text>
<checked>false</checked>
</item>
</jmolRadioGroup>
</jmol>

The active site cysteine can covalently bind to and unbind from the appropriate carbon on the dUMP-ring, as seen here in the analog of intermediate conformations. The conversion of the carboxylic oxygen of the folate to nitrogen (*) in the intermediate prevents the reaction from progressing to its products.

==Inhibition==
Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>
The image below shows tetrahydrofolic acid on the top and the inhibitor methotrexate on the bottom
[[Image:Methotrexate.png|400px]]
</StructureSection>

==3D structures of thymidylate synthase==
[[Thymidylate synthase 3D structures]]

== References ==
<references/>
[[Category:Topic Page]]
[[Category:Dihydrofolate]]
[[Category:One-carbon metabolism]]

Thymidylate synthase

2022-04-20T15:09:13Z

Shaylie Albright:

Thymidylate Synthase (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>

2-deoxyuridine-5'-monophosphate(dUMP) + 5, 10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F)

[[Image:TS Overview.jpg]]
== Function ==
'''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair<ref>PMID:2243092</ref>. In protozoa, [[dihydrofolate reductase]] (DHFR) and TS are expressed as a bifunctional monomeric enzyme ('''DHFR-TS)''' with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – '''ThyA''' and '''ThyX'''. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.

== Relevance ==
One of the nucleobase of DNA, cytosine, spontaneously deaminates to form uracil, changing the encoded message. Different from RNA, DNA does not contain uracil but instead contains the methylated form thymine, avoiding missense mutations. The [https://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair protein] [[Uracil DNA glycosylase]] will recognize uracil as damaged DNA, removing it and re-establishing the original message<ref>DOI:10.1038/sj.onc.1205996</ref>. Because thymine contains an additional methyl group, it is distinguishable from uracil, and is not removed through DNA repair. Thymidylate synthase helps to turn the abundant uridine (containing the nucleobase uracil) into deoxythymidine (containing the nucleobase thymine) in preparation for DNA synthesis prior to cell division. Thus, thymidylate synthase plays a role in making DNA a more reliable long-term storage of genetic information compared to RNA.

TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>

<StructureSection load='' size='350' side='right' caption='Thymidylate synthase complex with dUMP (PDB entry [[1tsv]])' scene='49/493689/Cv/1'>
==Structure and ligand binding==
TS forms a homodimer consisting of two domains (reload <scene name='49/493689/Cv/1'>initial scene</scene>). Their <scene name='49/493689/Cv/4'>active sites can each bind the substrate dUMP</scene><ref>PMID:9053905</ref>. Maley et al. show that E.coli TS uses a half-the-sites mechanism when catalyzing its reaction. One of the two active sites catalyzes the reaction while the other remains inactive. The way the two domains communicate with each other to coordinate this is still unknown.

The active site Cysteine has two <scene name='49/493689/Ts_7jxf_percentb/4'>conformations</scene>. Conformation 1 shows the active site cysteineunbound to the intermediate 4.21 Angstroms away from the C6 carbon of the dNMP ring. Conformation 2 shows the active site cysteine bound to the intermediate 3.84 Angstroms away from the C6 carbon of the dNMP ring.
<jmol>
<jmolRadioGroup>
<item>
<script>hide (VNM or 146:B) and altloc=A</script>
<text>Conformation 1</text>
<checked>true</checked>
</item>
<item>
<script>hide (VNM or 146:B) and altloc=B</script>
<text>Conformation 2</text>
<checked>false</checked>
</item>
<item>
<script>hide none</script>
<text>both conformations</text>
<checked>false</checked>
</item>
</jmolRadioGroup>
</jmol>
==Inhibition==
Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>

[[Image:Methotrexate.png|400px]]
</StructureSection>

==3D structures of thymidylate synthase==
[[Thymidylate synthase 3D structures]]

== References ==
<references/>
[[Category:Topic Page]]
[[Category:Dihydrofolate]]
[[Category:One-carbon metabolism]]

Thymidylate synthase

2022-04-20T15:08:19Z

Shaylie Albright:

Thymidylate Synthase (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>

2-deoxyuridine-5'-monophosphate(dUMP) + 5, 10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F)

[[Image:TS Overview.jpg]]
== Function ==
'''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair<ref>PMID:2243092</ref>. In protozoa, [[dihydrofolate reductase]] (DHFR) and TS are expressed as a bifunctional monomeric enzyme ('''DHFR-TS)''' with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – '''ThyA''' and '''ThyX'''. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.

== Relevance ==
One of the nucleobase of DNA, cytosine, spontaneously deaminates to form uracil, changing the encoded message. Different from RNA, DNA does not contain uracil but instead contains the methylated form thymine, avoiding missense mutations. The [https://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair protein] [[Uracil DNA glycosylase]] will recognize uracil as damaged DNA, removing it and re-establishing the original message<ref>DOI:10.1038/sj.onc.1205996</ref>. Because thymine contains an additional methyl group, it is distinguishable from uracil, and is not removed through DNA repair. Thymidylate synthase helps to turn the abundant uridine (containing the nucleobase uracil) into deoxythymidine (containing the nucleobase thymine) in preparation for DNA synthesis prior to cell division. Thus, thymidylate synthase plays a role in making DNA a more reliable long-term storage of genetic information compared to RNA.

TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>

<StructureSection load='' size='350' side='right' caption='Thymidylate synthase complex with dUMP (PDB entry [[1tsv]])' scene='49/493689/Cv/1'>
==Structure and ligand binding==
TS forms a homodimer consisting of two domains (reload <scene name='49/493689/Cv/1'>initial scene</scene>). Their <scene name='49/493689/Cv/4'>active sites can each bind the substrate dUMP</scene><ref>PMID:9053905</ref>. Maley et al. show that E.coli TS uses a half-the-sites mechanism when catalyzing its reaction. One of the two active sites catalyzes the reaction while the other remains inactive. The way the two domains communicate with each other to coordinate this is still unknown.

The active site Cysteine has two <scene name='49/493689/Ts_7jxf_percentb/4'>conformations</scene>. Conformation 1 shows the active site cysteineunbound to the intermediate 4.21 Angstroms away from the C6 carbon of the dNMP ring. Conformation 2 shows the active site cysteine bound to the intermediate 3.84 Angstroms away from the C6 carbon of the dNMP ring.
<jmol>
<jmolRadioGroup>
<item>
<script>hide (VNM or 146:B) and altloc=A</script>
<text>Conformation 1</text>
<checked>true</checked>
</item>
<item>
<script>hide (VNM or 146:B) and altloc=B</script>
<text>Conformation 2</text>
<checked>false</checked>
</item>
<item>
<script>hide none</script>
<text>both conformations</text>
<checked>false</checked>
</item>
</jmolRadioGroup>
</jmol>
==Inhibition==
Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>
</StructureSection>

[[Image:Methotrexate.png]]

==3D structures of thymidylate synthase==
[[Thymidylate synthase 3D structures]]

== References ==
<references/>
[[Category:Topic Page]]
[[Category:Dihydrofolate]]
[[Category:One-carbon metabolism]]

File:Methotrexate.png

2022-04-20T15:04:22Z

Shaylie Albright: molecular structure of methotrexate in comparison to folic acid

== Summary ==
molecular structure of methotrexate in comparison to folic acid
== Licensing ==
{{cc-by-sa-3.0}}

Thymidylate synthase

2022-04-20T14:44:21Z

Shaylie Albright:

Thymidylate Synthase (TS) is an important enzyme in [[one-carbon metabolism]]. TS catalyzes the transfer of a methyl group and a hydride from 5,10-methylenetetrahydrofolate to 2-deoxyuridine-5'-monophosphate, resulting in the formation of thymidine 5'-monophosphate and dihydrofolate. This is the only de novo source of dTMP (a precursor to Thymine) in humans. <ref>DOI 10.1021/acs.biochem.1c00063</ref>

2-deoxyuridine-5'-monophosphate(dUMP) + 5, 10-methylenetetrahydrofolate(CH<sub>2</sub>H<sub>4</sub>F) ⇌ thymidine 5'-monophosphate(dTMP) + Dihydrofolate(H<sub>2</sub>F)

[[Image:TS Overview.jpg]]
== Function ==
'''Thymidylate synthase''' (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylenetetrahydrofolate as a cofactor. TS is essential for DNA replication and repair<ref>PMID:2243092</ref>. In protozoa, [[dihydrofolate reductase]] (DHFR) and TS are expressed as a bifunctional monomeric enzyme ('''DHFR-TS)''' with the DHFR entity at the N terminal. DHFR and TS catalyze consecutive reactions in the dTMP biosynthesis. There are two different types of TS – '''ThyA''' and '''ThyX'''. The types differ in their activity and structure. The TS ThyX are flavin-dependent enzymes.

== Relevance ==
One of the nucleobase of DNA, cytosine, spontaneously deaminates to form uracil, changing the encoded message. Different from RNA, DNA does not contain uracil but instead contains the methylated form thymine, avoiding missense mutations. The [https://proteopedia.org/wiki/index.php/Category:Dna-repair DNA repair protein] [[Uracil DNA glycosylase]] will recognize uracil as damaged DNA, removing it and re-establishing the original message<ref>DOI:10.1038/sj.onc.1205996</ref>. Because thymine contains an additional methyl group, it is distinguishable from uracil, and is not removed through DNA repair. Thymidylate synthase helps to turn the abundant uridine (containing the nucleobase uracil) into deoxythymidine (containing the nucleobase thymine) in preparation for DNA synthesis prior to cell division. Thus, thymidylate synthase plays a role in making DNA a more reliable long-term storage of genetic information compared to RNA.

TS inhibition at its folate-binding site is used in anticancer therapeutic drugs. DHFR-TS inhibitors are potential drug targets against parasite-transferred diseases. TS exhibits oncogene-like activity.<ref>PMID:15093541</ref>

<StructureSection load='' size='350' side='right' caption='Thymidylate synthase complex with dUMP (PDB entry [[1tsv]])' scene='49/493689/Cv/1'>
==Structure and ligand binding==
Thymidylate synthase forms a dimer (reload <scene name='49/493689/Cv/1'>initial scene</scene>).
TS <scene name='49/493689/Cv/4'>active site contains the substrate dUMP</scene><ref>PMID:9053905</ref>. Water molecules are shown as red spheres.

The active site Cysteine has two <scene name='49/493689/Ts_7jxf_percentb/4'>conformations</scene>. Conformation 1 shows the active site cysteineunbound to the intermediate 4.21 Angstroms away from the C6 carbon of the dNMP ring. Conformation 2 shows the active site cysteine bound to the intermediate 3.84 Angstroms away from the C6 carbon of the dNMP ring.
<jmol>
<jmolRadioGroup>
<item>
<script>hide (VNM or 146:B) and altloc=A</script>
<text>Conformation 1</text>
<checked>true</checked>
</item>
<item>
<script>hide (VNM or 146:B) and altloc=B</script>
<text>Conformation 2</text>
<checked>false</checked>
</item>
<item>
<script>hide none</script>
<text>both conformations</text>
<checked>false</checked>
</item>
</jmolRadioGroup>
</jmol>
==Inhibition==
Methotrexate, a competitive inhibitor competes with folate substrate to bind to the active site of TS. Inhibits the conversion of CH<sub>2</sub>H<sub>4</sub>F to H<sub>2</sub>F. This inhibition stops the conversion of products to reactants, stopping cellular reproduction. <scene name='49/493689/Inhibited/1'>inhibits</scene> TS.

Due to its role in cell division, thymidylate synthase has become a popular target for anticancer drugs. Indirect inhibition of thymidylate synthase by the drug 5-fluorouracil (5-FU) is one of the most used inhibitors for study of TS function. This drug indirectly inhibits TS as it it eventually converted to FdUMP, which forms a covalent complex with both the active site cysteine and CH<sub>2</sub>H<sub>4</sub>F. Inhibition of TS halts the production of dTMP and, indirectly, 2'-deoxythymidine-5'-triphosphate (dTTP). Both dTMP and dTTP are essential building blocks for DNA synthesis and their absence halts the ability of cells to replicate their genetic information. This is especially effective in cancer cells that rapidly divide and require large amounts of dTMP and dTTP. <ref>DOI 10.2174/0929867054864868</ref>
</StructureSection>

==3D structures of thymidylate synthase==
[[Thymidylate synthase 3D structures]]

== References ==
<references/>
[[Category:Topic Page]]
[[Category:Dihydrofolate]]
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-15T14:50:17Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme is a regulatory agent of folate [[one-carbon metabolism]]. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

5,10-methylenetetrahydrofolate + NADPH + H+ <-> 5-methyltetrahydrofolate + NADP+

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.<ref>DOI: 10.1038/s41467-018-04735-2</ref>

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/2'>

== Structural highlights ==
{{Template:Button Toggle Animation2}}
MTHFR catalyzes the reaction using a <scene name='90/907473/Superposition/5'>ping pong mechanism</scene>, where a substrate binds and forms an intermediate before releasing the product, followed by the binding of a second substrate and later release of a second product <ref>DOI:10.1021/bi9007325</ref>.

</StructureSection>
== References ==
<references/>
[[Category:One-carbon metabolism]]

Methylenetetrahydrofolate reductase

2022-04-13T15:23:42Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme is a regulatory agent of one carbon folate metabolism. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/5'>ping pong mechanism</scene>
{{Template:Button Toggle Animation2}}

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/>

Methylenetetrahydrofolate reductase

2022-04-13T15:20:44Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme is a regulatory agent of one carbon folate metabolism. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/5'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-13T15:11:03Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme is a regulatory agent of one carbon folate metabolism. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-13T15:10:01Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme.

[[Image:MTHFR Reaction.jpg|800px]]

MTHFR is an enzyme is a regulatory agent of one carbon folate metabolism. The enzyme is present in both eukaryotes and prokaryotes however, the structure is unique in eukaryotes as it has a SAM binding domain. The enzyme has an essential role in S-Adenosyl Methionine (SAM) regulation in order to promote homeostasis within the folate cycle. This shows the importance of MTHFR within the human body, and identifies the issues that may arise if MTHFR dysfunction occurs.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-11T15:15:36Z

Shaylie Albright:

[[Methylenetetrahydrofolate reductase]] (MTHFR) is an enzyme.

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Talk:MTHFR

2022-04-11T15:13:48Z

Shaylie Albright: Talk:MTHFR moved to Talk:Methylenetetrahydrofolate reductase

#REDIRECT [[Talk:Methylenetetrahydrofolate reductase]]

Talk:Methylenetetrahydrofolate reductase

2022-04-11T15:13:48Z

Shaylie Albright: Talk:MTHFR moved to Talk:Methylenetetrahydrofolate reductase

Textbook chapter on folate reactions: [https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_v2.0_(Soderberg)/17%3A_The_Organic_Chemistry_of_Vitamins/17.05%3A_Folate Chapter 17.5]

Textbook on ping pong mechanisms: [https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_(Biological_Chemistry)/Enzymes/Enzymatic_Kinetics/Ping-pong_mechanisms Libretext again]

1ZP3, 1ZP4, 1ZPT, and 1ZRQ are the E. coli structures with substrate or product bound.

The paper is behind a paywall, but here is the link to the abstract: [https://pubs.acs.org/doi/abs/10.1021/bi050533q]

Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition<ref>DOI:10.1038/s41467-018-04735-2</ref>

Biochemistry of the enzyme: https://www.researchgate.net/profile/Elizabeth-Trimmer/publication/232764343_Methylenetetrahydrofolate_Reductase_Biochemical_Characterization_and_Medical_Significance/links/5541077d0cf232222731506c/Methylenetetrahydrofolate-Reductase-Biochemical-Characterization-and-Medical-Significance.pdf
==Your Heading Here (maybe something like 'Structure')==
<StructureSection load='3rec' size='350' side='right' caption='Escherichia coli reca protein-bound DNA (PDB entry [[3rec]])' scene=''>

Anything in this section will appear adjacent to the 3D structure and will be scrollable. <scene name='90/907477/Superposition/1'>Superposition</scene>

</StructureSection>

5 methyl folate as dietary supplement: [https://en.wikipedia.org/wiki/Levomefolic_acid]

Making the supplement: [https://patents.google.com/patent/US20120315679A1/en]

<ref>DOI:10.1093/aje/kwj347</ref>

<ref>DOI:10.1007/s10897-016-9956-7 </ref>
<references/>

MTHFR

2022-04-11T15:13:47Z

Shaylie Albright: MTHFR moved to Methylenetetrahydrofolate reductase

#REDIRECT [[Methylenetetrahydrofolate reductase]]

Methylenetetrahydrofolate reductase

2022-04-11T15:13:47Z

Shaylie Albright: MTHFR moved to Methylenetetrahydrofolate reductase

[[MTHFR]] is an enzyme.

[[Image:MTHFR Reaction.jpg|800px]]

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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 talk:Shaylie Albright/MTHFR

2022-04-11T15:13:28Z

Shaylie Albright: User talk:Shaylie Albright/MTHFR moved to Talk:MTHFR

#REDIRECT [[Talk:MTHFR]]

Talk:Methylenetetrahydrofolate reductase

2022-04-11T15:13:28Z

Shaylie Albright: User talk:Shaylie Albright/MTHFR moved to Talk:MTHFR

User:Shaylie Albright/MTHFR

2022-04-11T15:13:28Z

Shaylie Albright: User:Shaylie Albright/MTHFR moved to MTHFR

#REDIRECT [[MTHFR]]

Methylenetetrahydrofolate reductase

2022-04-11T15:13:28Z

Shaylie Albright: User:Shaylie Albright/MTHFR moved to MTHFR

Methylenetetrahydrofolate reductase

2022-04-11T15:12:27Z

Shaylie Albright:

File:MTHFR Reaction.jpg

2022-04-11T14:53:56Z

Shaylie Albright: The reduction of 5,10 MTHF to 5 MTHF catalyzed by the enzyme MTHFR

== Summary ==
The reduction of 5,10 MTHF to 5 MTHF catalyzed by the enzyme MTHFR
== Licensing ==
{{self|cc-by-sa-3.0|GFDL}}

File:MTHFR2DImage-images.zip

2022-04-11T14:44:04Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-04-06T15:12:58Z

Shaylie Albright:

[[MTHFR]] is an enzyme.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-06T15:12:35Z

Shaylie Albright:

[MTHFR] is an enzyme.

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-06T15:09:52Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

== Function ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

<StructureSection load='' size='340' side='right' scene='90/907473/Mthfr_protein/1'>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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.
== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-06T15:05:28Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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 ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
In addition to the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-06T15:04:54Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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 ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
Aside from the folate cycle, MTHFR is also a major component of the homeostasis of homocysteine in the blood stream. When this homeostasis is disrupted, mutations are created that result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia. Hyperhomocysteinemia is an excess of the amino acid circulating in the body, and is a direct correlation of cardiovascular disease, Alzheimer's disease, depression, and neural tube defects within the fetus. Furthermore, homocystinuria is clinically described as the body's inability to adequately process homocysteine and the amino acid methionine. This dysfunction can be clinically presented with skeletal, vision, and blood clotting abnormalities coupled with learning disorders.

== Relevance ==

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-06T14:40:13Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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 ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==
Association with disease is prevalent with the enzyme. If the human body is deficient of MTHFR, it can result in hyperhomocysteinemia with homocystinuria, or mild hyperhomocysteinemia.

== Relevance ==

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-05T18:34:22Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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 ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and the second substrate nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==

== Relevance ==

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-05T18:30:14Z

Shaylie Albright:

==MTHFR==
<scene name='90/907473/Mthfr_protein/1'>first scene</scene>

<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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 ==
Methylenetetrahydrofolate reductase (MTHFR) is a regulatory agent of one carbon folate metabolism. The enzyme catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate to be recycled back into the folate cycle, and for aiding folate uptake in the body. This reduction reaction requires the cofactor molecule flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor in the reaction. MTHFR has a unique folding structure. Its N-terminal is abundant in serine and acts as a phosphorylation site, its situated in close proximity to it's C-terminal S-adenosyl methionine (SAM) binding site. A linker joins the catalytic domain (N-terminal) to the regulatory domain (C-terminal) for interaction and increases the sensitivity to SAM binding and feedback properties.

== Disease ==

== Relevance ==

== Structural highlights ==
MTHFR<scene name='90/907473/Superposition/4'>ping pong mechanism</scene>
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/>

Methylenetetrahydrofolate reductase

2022-04-05T18:14:43Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-04-05T18:01:41Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-04-05T17:58:48Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-04-05T17:57:37Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-04-05T17:56:26Z

Shaylie Albright:

File:6fcx.pdb

2022-04-05T17:39:12Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-03-18T15:17:41Z

Shaylie Albright:

Methylenetetrahydrofolate reductase

2022-03-18T15:00:20Z

Shaylie Albright: New page: ==MTHFR== <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> This is a default text for your page '''Shaylie Albright/MTHFR'''. Click abov...

==MTHFR==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page '''Shaylie Albright/MTHFR'''. 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/>