Thymidylate synthase - Revision history

Wu3857: /* Reference */

2019-08-19T23:17:14Z

‎Reference

Wu3857 at 20:53, 29 July 2019

2019-07-29T20:53:33Z

Wu3857: /* Protein Function */

2019-07-29T03:03:04Z

‎Protein Function

Wu3857: /* Protein Function */

2019-07-29T03:02:40Z

‎Protein Function

Wu3857: /* Protein Function */

2019-07-29T03:02:30Z

‎Protein Function

Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF..."

2019-07-29T02:53:17Z

Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF..."

New page

{| align="left"
| __TOC__
|}
{{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF00303 Thymidylate synthase family]|[[:Category:Thymidylate synthase|Ligand list]]}}
==Summary==

===Protein Function ===
Thymidylate synthetase (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). dTMP is one of the three nucleotides (dTMP, dTTP, and dTDP) that form thymine. Thymine is a nucleic acid in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUTP arise. Both cause DNA damage.The following reaction catalyzed by thymidylate synthetase: 
5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP 
This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the four DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates. (From Wikipedia) 

===Cys Function & Property===
Cys195 is the active site of Thymidylate synthase, act as nucleophile. 

* Hydrophobic property:
:[[File:493-hydro.png||600px]]
* SASA：
:Cys195: 25.299 A^2

==Protein Sequence==

MPVAGSELPR RPLPPAAQER DAEPRPPHGE LQYLGQIQHI LRCGVRKDDR 
TGTGTLSVFG MQARYSLRDE FPLLTTKRVF WKGVLEELLW FIKGSTNAKE 
LSSKGVKIWD ANGSRDFLDS LGFSTREEGD LGPVYGFQWR HFGAEYRDME 
SDYSGQGVDQ LQRVIDTIKT NPDDRRIIMC AWNPRDLPLM ALPP'''C'''HALCQ 
FYVVNSELSC QLYQRSGDMG LGVPFNIASY ALLTYMIAHI TGLKPGDFIH 
TLGDAHIYLN HIEPLKIQLQ REPRPFPKLR ILRKVEKIDD FKAEDFQIEG 
YNPHPTIKME MAV 


==Structural Information==
*Known structures with covalent ligands: 
:Unknown 

*Protein structure:
[[File:493.png|center|800px]]

==Related Pathway==
*[https://www.genome.jp/kegg-bin/show_pathway?ko00240 Pyrimidine metabolism] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko00670 One carbon pool by folate] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko01100 Metabolic pathways] 
*[https://www.genome.jp/kegg-bin/show_pathway?ko01523 Antifolate resistance] 

==Experimental Evidence==
:MALDI-MS, Tryptic Digest

==Reference==
# Nonoo R H, Armstrong A, Mann D J. '''Kinetic Template‐Guided Tethering of Fragments[J].''' ChemMedChem, 2012, 7(12): 2082-2086. [https://www.ncbi.nlm.nih.gov/pubmed/?term=23033251 23033251] 

[[Category:Targets|Targets]]
[[Category:Homo sapiens|Homo sapiens]]
[[Category:Thymidylate synthase family|Thymidylate synthase family]]
[[Category:Pyrimidine metabolism|Pyrimidine metabolism]]
[[Category:One carbon pool by folate|One carbon pool by folate]]
[[Category:Metabolic pathways|Metabolic pathways]]
[[Category:Antifolate resistance|Antifolate resistance]]

@@ Line 48: / Line 48: @@
 # Nonoo R H, Armstrong A, Mann D J. '''Kinetic Template‐Guided Tethering of Fragments[J].''' ChemMedChem, 2012, 7(12): 2082-2086. [https://www.ncbi.nlm.nih.gov/pubmed/?term=23033251 23033251]<br/>
-[[Category:Targets|Targets]]
+[[Category:Targets]]
-[[Category:Homo sapiens|Homo sapiens]]
+[[Category:Homo sapiens]]
-[[Category:Metabolic enzyme|Metabolic enzyme]]
+[[Category:Metabolic enzyme]]
-[[Category:Thymidylate synthase family|Thymidylate synthase family]]
+[[Category:Thymidylate synthase family]]
-[[Category:Pyrimidine metabolism|Pyrimidine metabolism]]
+[[Category:Pyrimidine metabolism]]
-[[Category:One carbon pool by folate|One carbon pool by folate]]
+[[Category:One carbon pool by folate]]
-[[Category:Metabolic pathways|Metabolic pathways]]
+[[Category:Metabolic pathways]]
-[[Category:Antifolate resistance|Antifolate resistance]]
+[[Category:Antifolate resistance]]

@@ Line 7: / Line 7: @@
 ===Protein Function ===
 Thymidylate synthetase (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). dTMP is one of the three nucleotides (dTMP, dTTP, and dTDP) that form thymine. Thymine is a nucleic acid in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUTP arise. Both cause DNA damage.The following reaction catalyzed by thymidylate synthetase:<br/>
-<div align="center">5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP</div>
+:::::::5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP<br/>
 This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the four DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates. (From Wikipedia)<br/>

@@ Line 7: / Line 7: @@
 ===Protein Function ===
 Thymidylate synthetase (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). dTMP is one of the three nucleotides (dTMP, dTTP, and dTDP) that form thymine. Thymine is a nucleic acid in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUTP arise. Both cause DNA damage.The following reaction catalyzed by thymidylate synthetase:<br/>
-<div align="center">5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP</div><br/>
+<div align="center">5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP</div>
 This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the four DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates. (From Wikipedia)<br/>

@@ Line 7: / Line 7: @@
 ===Protein Function ===
 Thymidylate synthetase (EC 2.1.1.45) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). dTMP is one of the three nucleotides (dTMP, dTTP, and dTDP) that form thymine. Thymine is a nucleic acid in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUTP arise. Both cause DNA damage.The following reaction catalyzed by thymidylate synthetase:<br/>
-,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP<br/>
+<div align="center">5,10-methylenetetrahydrofolate + dUMP ↔ dihydrofolate + dTMP</div><br/>
 This provides the sole de novo pathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer. The enzyme is essential for regulating the balanced supply of the four DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process cause various biological and genetic abnormalities, such as thymineless death. Thymidylate synthase is an enzyme of about 30 to 35 Kd in most species except in protozoan and plants where it exists as a bifunctional enzyme that includes a dihydrofolate reductase domain. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates. (From Wikipedia)<br/>

@@ Line 2: / Line 2: @@
    | __TOC__
    |}
-{{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF00303 Thymidylate synthase family]|[[:Category:Thymidylate synthase|Ligand list]]}}
+{{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF00303 Thymidylate synthase family]|[[:Category:Thymidylate synthase|Ligand list]]|Metabolic enzyme}}
 ==Summary==
@@ Line 50: / Line 50: @@
 [[Category:Targets|Targets]]
 [[Category:Homo sapiens|Homo sapiens]]
 [[Category:Thymidylate synthase family|Thymidylate synthase family]]
 [[Category:Pyrimidine metabolism|Pyrimidine metabolism]]

Thymidylate synthase - Revision history

Wu3857: /* Reference */

Wu3857 at 20:53, 29 July 2019

Wu3857: /* Protein Function */

Wu3857: /* Protein Function */

Wu3857: /* Protein Function */

Wu3857: Created page with "{| align="left" | __TOC__ |} {{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF..."

Wu3857: Created page with "{| align="left" | TOC |} {{#invoke:InfoboxforTarget|run|TSase, TYMS|[https://www.uniprot.org/uniprot/P04818 P04818]|Homo sapiens|Cys195|[http://pfam.xfam.org/family/PF..."