en>Monkbot: /* References */Fix CS1 deprecated date parameter errors

2014-01-21T23:53:20Z

References: Fix CS1 deprecated date parameter errors

← Older revision		Revision as of 01:53, 22 January 2014
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	~~Hello~~. ~~Allow me introduce~~ the ~~writer~~. ~~Her~~ name is ~~Emilia Shroyer but it's not~~ the ~~most feminine~~ title ~~out there~~. ~~Since she was eighteen she's been operating~~ as a ~~meter reader but she's always wanted her own business~~. ~~Body building~~ is ~~one~~ of ~~the things I adore most~~. ~~For~~ a ~~while I've been~~ in ~~South Dakota~~ and ~~my mothers~~ and ~~fathers live nearby~~.<br>~~<br>My web site~~: [http://www.~~zs-imports~~.~~com~~/~~blogs~~/~~post~~/~~70017 http:~~//~~www~~.zs-~~imports~~.~~com~~]		{{PBB\|geneid=7298}}
			{{enzyme
			\| Name = thymidylate synthase
			\| EC_number = 2.1.1.45
			\| CAS_number = 9031-61-2
			\| IUBMB_EC_number = 2/1/1/45
			\| GO_code = 0050757
			\| image =
			\| width =
			\| caption =
			}}
			{{Pfam_box
			\| Symbol = Thymidylat_synt
			\| Name = Thymidylate synthase
			\| image =
			\| width =
			\| caption =
			\| Pfam= PF00303
			\| InterPro= IPR000398
			\| SMART=
			\| Prosite = PDOC00086
			\| SCOP = 1tys
			\| TCDB =
			\| OPM family=
			\| OPM protein=
			}}
			'''Thymidylate synthetase''' ({{EC number\|2.1.1.45}})<ref>{{cite web \| title = Entrez Gene: TYMS thymidylate synthetase\| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7298\| accessdate = }}</ref> is the [[enzyme]] used to generate [[thymidine monophosphate]] (dTMP), which is subsequently [[Phosphorilation\|phosphorylated]] to [[thymidine triphosphate]] for use in [[DNA]] synthesis and repair.

			== Function ==

			The following reaction catalyzed by thymidylate synthetase:

			: 5,10-methylenetetrahydrofolate + dUMP <math>\rightleftharpoons</math> dihydrofolate + dTMP

			By means of reductive [[methylation]], [[deoxyuridine monophosphate]] (dUMP) and [[N5,N10-methylene tetrahydrofolate]] are together used to form dTMP, yielding [[dihydrofolate]] as a secondary product.

			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.<ref name="PUB00005100">{{cite journal \|author=Stroud RM, Santi DV, Hardy LW, Montfort WR, Jones MO, Finer-Moore JS \|title=Atomic structure of thymidylate synthase: target for rational drug design \|journal=Science \|volume=235 \|issue=4787 \|pages=448–455 \|year=1987 \|pmid=3099389 \|doi=10.1126/science.3099389}}</ref> The enzyme is essential for regulating the balanced supply of the 4 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.<ref name="PUB00002591">{{cite journal \|author=Gotoh O, Shimizu K, Kaneda S, Nalbantoglu J, Takeishi K, Seno T, Ayusawa D \|title=Structural and functional analysis of the human thymidylate synthase gene \|journal=J. Biol. Chem. \|volume=265 \|issue=33 \|pages=20277–20284 \|year=1990 \|pmid=2243092}}</ref> The enzyme is an important target for certain chemotherapeutic drugs. 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.<ref name="PUB00005100" /> 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.

			Thymidylate synthase is induced by a transcription factor LSF/[[TFCP2]] and LSF is an [[oncogene]] in [[hepatocellular carcinoma]]. LSF and Thymidylate synthase plays significant role in Liver Cancer proliferation and progression and Drug resistance.<ref name="Santhekadur_2012">{{cite journal \| author = Santhekadur PK, Rajasekaran D, Siddiq A, Gredler R, Chen D, Schaus SC, Hansen U, Fisher PB, Sarkar D \| year = 2012 \| title = The transcription factor LSF: a novel oncogene for hepatocellular carcinoma \| journal = Am J Cancer Res \| volume = 2 \| issue = 3 \| pages = 269–285 \| doi = \| pmid = \| pmc = \| url = http://www.ajcr.us/files/ajcr0000110.pdf }}</ref>

			== Clinical significance ==

			As an anti-cancer [[chemotherapy]] target, thymidylate synthetase can be inhibited by the [[thymidylate synthase inhibitor]]s such as fluorinated pyrimidine [[fluorouracil]], or certain [[folate]] [[analog (chemistry)\|analogues]], the most notable one being [[raltitrexed]] (trade name Tomudex).

			== Interactive pathway map ==
			{{FluoropyrimidineActivity WP1601\|highlight=Thymidylate_synthase}}

			==See also==
			* [[Antimetabolite#Pyrimidine analogues\|Pyrimidine analogues]]
			* [[Thymidylate synthase inhibitor]]

			==References==
			{{reflist}}

			==Further reading==
			{{refbegin \| 2}}
			*{{cite journal \| author= Carreras CW, and Santi DV \|title=The Catalytic Mechanism and Structure of Thymidylate Synthase \|journal=Annual Review of Biochemistry \|volume=64 \|issue= 1 \|pages= 721–762 \|year= 1995 \|pmid= 7574499 \|doi=10.1146/annurev.bi.64.070195.003445 }}
			*{{cite journal \| author=Banerjee D \|title=Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase \|journal=Biochim. Biophys. Acta \|volume=1587 \|issue= 2–3 \|pages= 164–73 \|year= 2002 \|pmid= 12084458 \|doi= 10.1016/S0925-4439(02)00079-0\| author-separator=, \| author2=Mayer-Kuckuk P \| author3=Capiaux G \| display-authors=3 \| last4=Budak-Alpdogan \| first4=T \| last5=Gorlick \| first5=R \| last6=Bertino \| first6=JR }}
			*{{cite journal \| author=Liu J \|title=Thymidylate synthase as a translational regulator of cellular gene expression \|journal=Biochim. Biophys. Acta \|volume=1587 \|issue= 2–3 \|pages= 174–82 \|year= 2002 \|pmid= 12084459 \|doi= \| author-separator=, \| author2=Schmitz JC \| author3=Lin X \| display-authors=3 \| last4=Tai \| first4=N \| last5=Yan \| first5=W \| last6=Farrell \| first6=M \| last7=Bailly \| first7=M \| last8=Chen \| first8=T \| last9=Chu \| first9=E }}
			*{{cite journal \| author=Chu J, Dolnick BJ \|title=Natural antisense (rTSalpha) RNA induces site-specific cleavage of thymidylate synthase mRNA \|journal=Biochim. Biophys. Acta \|volume=1587 \|issue= 2–3 \|pages= 183–93 \|year= 2002 \|pmid= 12084460 \|doi= }}
			*{{cite journal \| author=Peters GJ \|title=Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism \|journal=Biochim. Biophys. Acta \|volume=1587 \|issue= 2–3 \|pages= 194–205 \|year= 2002 \|pmid= 12084461 \|doi= \| author-separator=, \| author2=Backus HH \| author3=Freemantle S \| display-authors=3 \| last4=Van Triest \| first4=B \| last5=Codacci-Pisanelli \| first5=G \| last6=Van Der Wilt \| first6=CL \| last7=Smid \| first7=K \| last8=Lunec \| first8=J \| last9=Calvert \| first9=AH }}
			*{{cite journal \| author=Costi MP \|title=Structure-based studies on species-specific inhibition of thymidylate synthase \|journal=Biochim. Biophys. Acta \|volume=1587 \|issue= 2–3 \|pages= 206–14 \|year= 2002 \|pmid= 12084462 \|doi= \| author-separator=, \| author2=Tondi D \| author3=Rinaldi M \| display-authors=3 \| last4=Barlocco \| first4=D \| last5=Pecorari \| first5=P \| last6=Soragni \| first6=F \| last7=Venturelli \| first7=A \| last8=Stroud \| first8=RM }}
			*{{cite journal \| author=Lin D \|title=Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development \|journal=Forum of nutrition \|volume=60 \|issue= \|pages= 140–5 \|year= 2007 \|pmid= 17684410 \|doi=10.1159/000107090 \| author-separator=, \| author2=Li H \| author3=Tan W \| display-authors=3 \| series=Forum of Nutrition \| last4=Miao \| first4=Xiaoping \| last5=Wang \| first5=Li \| isbn=3-8055-8216-1 }}
			{{refend}}

			==External links==
			* {{MeshName\|Thymidylate+synthetase}}

			{{PDB Gallery\|geneid=7298}}
			{{Methyltransferases}}
			{{Nucleotide metabolism}}

			{{DEFAULTSORT:Thymidylate Synthase}}
			[[Category:EC 2.1.1]]

en>Teuxe: /* See also */ Replaced "-" by minor sign "−"

2011-09-02T16:39:59Z

See also: Replaced "-" by minor sign "−"

New page

Hello. Allow me introduce the writer. Her name is Emilia Shroyer but it's not the most feminine title out there. Since she was eighteen she's been operating as a meter reader but she's always wanted her own business. Body building is one of the things I adore most. For a while I've been in South Dakota and my mothers and fathers live nearby.<br><br>My web site: [http://www.zs-imports.com/blogs/post/70017 http://www.zs-imports.com]

Infinite arithmetic series - Revision history

en>Monkbot: /* References */Fix CS1 deprecated date parameter errors

en>Teuxe: /* See also */ Replaced "-" by minor sign "−"