User:Madelyn Kasprzak/Sandbox 6 - Revision history

Madelyn Kasprzak at 04:59, 28 April 2016

Madelyn Kasprzak — Thu, 28 Apr 2016 04:59:23 GMT

←Older revision		Revision as of 04:59, 28 April 2016
Line 7:		Line 7:
	<div style="width:66%;float:left;">		<div style="width:66%;float:left;">

-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three <scene name='72/728164/Two_iron_binding_residues/1'>Fe~~<sup>2+</sup>~~ binding sites</scene> and an <scene name='72/728164/2-oxoglutarate_binding_site/1'>α-ketoglutarate binding site</scene>.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region perform the main catalytic activity for these enzymes.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three <scene name='72/728164/Two_iron_binding_residues/1'>Fe(II) binding sites</scene> and an <scene name='72/728164/2-oxoglutarate_binding_site/2'>α-ketoglutarate binding site</scene>.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region perform the main catalytic activity for these enzymes.

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />

Madelyn Kasprzak: added two green links for iron binding and 2-oxoglutarate binding residues

Madelyn Kasprzak — Thu, 28 Apr 2016 04:47:52 GMT

added two green links for iron binding and 2-oxoglutarate binding residues

←Older revision		Revision as of 04:47, 28 April 2016
Line 7:		Line 7:
	<div style="width:66%;float:left;">		<div style="width:66%;float:left;">

-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region perform the main catalytic activity for these enzymes.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three <scene name='72/728164/Two_iron_binding_residues/1'>Fe<sup>2+</sup> binding sites</scene> and an <scene name='72/728164/2-oxoglutarate_binding_site/1'>α-ketoglutarate binding site</scene>.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region perform the main catalytic activity for these enzymes.

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />

Madelyn Kasprzak at 18:23, 27 April 2016

Madelyn Kasprzak — Wed, 27 Apr 2016 18:23:11 GMT

←Older revision		Revision as of 18:23, 27 April 2016
Line 7:		Line 7:
	<div style="width:66%;float:left;">		<div style="width:66%;float:left;">

-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region perform the main catalytic activity for these enzymes.

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
Line 14:		Line 14:
	<StructureSection load='5d9y' size='335' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>		<StructureSection load='5d9y' size='335' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>
	</div>		</div>
-

	</div>		</div>
		+
		+

	== Function ==		== Function ==
Line 25:		Line 26:
	While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli & Yi Zhang'>DOI 10.1038/nature12750</ref>		While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli & Yi Zhang'>DOI 10.1038/nature12750</ref>

-	[[Image:nsmb.2437-F1.jpg\|~~400px~~\|left\|thumb\|Cycle of DNA methylation and demethylation by DNA methyltransferases (DNMTs) and TET proteins.<ref>DOI 10.1038/nsmb.2437</ref>]]	+	[[Image:nsmb.2437-F1.jpg\|395px\|left\|thumb\|Cycle of DNA methylation and demethylation by DNA methyltransferases (DNMTs) and TET proteins.<ref>DOI 10.1038/nsmb.2437</ref>]]

	===Specific Functions===		===Specific Functions===

Madelyn Kasprzak at 18:11, 27 April 2016

Madelyn Kasprzak — Wed, 27 Apr 2016 18:11:46 GMT

←Older revision		Revision as of 18:11, 27 April 2016
Line 12:		Line 12:
	</div>		</div>
	<div style="width:33%;float:right;clear:right;border:1px solid black;">		<div style="width:33%;float:right;clear:right;border:1px solid black;">
-	<StructureSection load='5d9y' size='~~333~~' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>	+	<StructureSection load='5d9y' size='335' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>
	</div>		</div>

Line 40:		Line 40:

	Point mutations within the TET1 isoform can lead to a loss of enzyme function which causes a lack of DNA demethylation; two occur at the 1672 and 1674 amino acid residues, the first being a H1672Y mutation and the second being a D1674A mutation. A severe mutation in the 1608-1609 codons can lead to TET1 becoming an oncogene in acute leukemias. This mutation fuses TET1 and KMT2A/MLL1 to form an oncogene.<ref>PMID:12124344</ref><ref>PMID:12646957</ref>		Point mutations within the TET1 isoform can lead to a loss of enzyme function which causes a lack of DNA demethylation; two occur at the 1672 and 1674 amino acid residues, the first being a H1672Y mutation and the second being a D1674A mutation. A severe mutation in the 1608-1609 codons can lead to TET1 becoming an oncogene in acute leukemias. This mutation fuses TET1 and KMT2A/MLL1 to form an oncogene.<ref>PMID:12124344</ref><ref>PMID:12646957</ref>
-

	=== TET2 Isoform ===		=== TET2 Isoform ===

Madelyn Kasprzak at 18:10, 27 April 2016

Madelyn Kasprzak — Wed, 27 Apr 2016 18:10:00 GMT

←Older revision		Revision as of 18:10, 27 April 2016
Line 5:		Line 5:
	<div style="width:auto;clear:both;">		<div style="width:auto;clear:both;">
	== Structure ==		== Structure ==
-	<div style="width:50%;float:left;">	+	<div style="width:66%;float:left;">

	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.		The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.
Line 11:		Line 11:
	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
	</div>		</div>
-	<div style="width:45%;float:right;clear:right;border:1px solid black;">	+	<div style="width:33%;float:right;clear:right;border:1px solid black;">
-	<StructureSection load='5d9y' size='~~360~~' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>	+	<StructureSection load='5d9y' size='333' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>
	</div>		</div>
		+
		+
	</div>		</div>

Madelyn Kasprzak at 18:01, 27 April 2016

Madelyn Kasprzak — Wed, 27 Apr 2016 18:01:36 GMT

←Older revision		Revision as of 18:01, 27 April 2016
Line 3:		Line 3:
	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (<scene name='72/728164/Naegleria_gruberi_tet1/1'>TET1</scene>), methylcytosine dioxygenase <scene name='72/728164/Human_tet2_5fc/1'>TET2</scene>, and methylcytosine dioxygenase <scene name='72/728164/Xenopus_tropicalis_tet3_dna/1'>TET3</scene>. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (<scene name='72/728164/Naegleria_gruberi_tet1/1'>TET1</scene>), methylcytosine dioxygenase <scene name='72/728164/Human_tet2_5fc/1'>TET2</scene>, and methylcytosine dioxygenase <scene name='72/728164/Xenopus_tropicalis_tet3_dna/1'>TET3</scene>. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

-	<~~StructureSection load~~=~~'5d9y' size='400' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''~~>	+	<div style="width:auto;clear:both;">
-		+
	== Structure ==		== Structure ==
		+	<div style="width:50%;float:left;">
		+
	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.		The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
-		+	</div>
-	</StructureSection>	+	<div style="width:45%;float:right;clear:right;border:1px solid black;">
		+	<StructureSection load='5d9y' size='360' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''></StructureSection>
		+	</div>
		+	</div>

	== Function ==		== Function ==
Line 34:		Line 38:

	Point mutations within the TET1 isoform can lead to a loss of enzyme function which causes a lack of DNA demethylation; two occur at the 1672 and 1674 amino acid residues, the first being a H1672Y mutation and the second being a D1674A mutation. A severe mutation in the 1608-1609 codons can lead to TET1 becoming an oncogene in acute leukemias. This mutation fuses TET1 and KMT2A/MLL1 to form an oncogene.<ref>PMID:12124344</ref><ref>PMID:12646957</ref>		Point mutations within the TET1 isoform can lead to a loss of enzyme function which causes a lack of DNA demethylation; two occur at the 1672 and 1674 amino acid residues, the first being a H1672Y mutation and the second being a D1674A mutation. A severe mutation in the 1608-1609 codons can lead to TET1 becoming an oncogene in acute leukemias. This mutation fuses TET1 and KMT2A/MLL1 to form an oncogene.<ref>PMID:12124344</ref><ref>PMID:12646957</ref>
		+

	=== TET2 Isoform ===		=== TET2 Isoform ===

Madelyn Kasprzak: changed viewer size

Madelyn Kasprzak — Wed, 27 Apr 2016 17:38:28 GMT

changed viewer size

←Older revision		Revision as of 17:38, 27 April 2016
Line 3:		Line 3:
	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (<scene name='72/728164/Naegleria_gruberi_tet1/1'>TET1</scene>), methylcytosine dioxygenase <scene name='72/728164/Human_tet2_5fc/1'>TET2</scene>, and methylcytosine dioxygenase <scene name='72/728164/Xenopus_tropicalis_tet3_dna/1'>TET3</scene>. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (<scene name='72/728164/Naegleria_gruberi_tet1/1'>TET1</scene>), methylcytosine dioxygenase <scene name='72/728164/Human_tet2_5fc/1'>TET2</scene>, and methylcytosine dioxygenase <scene name='72/728164/Xenopus_tropicalis_tet3_dna/1'>TET3</scene>. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

-	<StructureSection load='5d9y' size='~~320~~' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''>	+	<StructureSection load='5d9y' size='400' side='right' caption='Human TET2 in complex with DNA containing 5fC.' scene=''>

	== Structure ==		== Structure ==

Madelyn Kasprzak: altered page layout

Madelyn Kasprzak — Wed, 27 Apr 2016 17:35:29 GMT

altered page layout

←Older revision		Revision as of 17:35, 27 April 2016
Line 9:		Line 9:

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
		+
		+	</StructureSection>

	== Function ==		== Function ==
Line 51:		Line 53:
	Here some of the major residues of the <scene name='72/728166/5d9y_catalytic_site/1'>catalytic site</scene> are highlighted. The light green residues are 2-oxoglutarate binding residues, the orange residue binds the substrate, and the blue residue binds the catalytic iron ion. For the rest of the protein, only the backbone is shown in light gray.		Here some of the major residues of the <scene name='72/728166/5d9y_catalytic_site/1'>catalytic site</scene> are highlighted. The light green residues are 2-oxoglutarate binding residues, the orange residue binds the substrate, and the blue residue binds the catalytic iron ion. For the rest of the protein, only the backbone is shown in light gray.

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

Madelyn Kasprzak at 17:17, 27 April 2016

Madelyn Kasprzak — Wed, 27 Apr 2016 17:17:27 GMT

←Older revision		Revision as of 17:17, 27 April 2016
Line 6:		Line 6:

	== Structure ==		== Structure ==
-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> ~~This~~ DSBH domain~~, along with~~ the preceding cysteine-rich region, ~~performs~~ the main catalytic activity of these enzymes ~~and more generally, for all α-ketoglutarate oxygenases~~.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> For all α-ketoglutarate oxygenases, including TET enzymes, the DSBH domain and the preceding cysteine-rich region, perform the main catalytic activity for these enzymes.

	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />

Madelyn Kasprzak: Added short description to structural highlights section

Madelyn Kasprzak — Thu, 14 Apr 2016 08:05:18 GMT

Added short description to structural highlights section

←Older revision		Revision as of 08:05, 14 April 2016
Line 38:		Line 38:

	== Structural highlights ==		== Structural highlights ==
		+
		+	The following highlights are of the Human TET2 enzyme in complex with DNA.

	<scene name='72/728166/5d9y_helices_red/1'>Alpha helices</scene> are colored red.		<scene name='72/728166/5d9y_helices_red/1'>Alpha helices</scene> are colored red.