Sandbox GGC15 - Revision history

Student at 19:40, 28 April 2021

Student — Wed, 28 Apr 2021 19:40:40 GMT

←Older revision		Revision as of 19:40, 28 April 2021
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	'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''		'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''

-	[[Image:~~Active Site 3PM~~.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>	+	[[Image:Active_Site_3_PM.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>

	[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />		[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />

Student at 19:39, 28 April 2021

Student — Wed, 28 Apr 2021 19:39:14 GMT

←Older revision		Revision as of 19:39, 28 April 2021
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	'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''		'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''

-	[[Image:Active Site 3.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>	+	[[Image:Active Site 3PM.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>

	[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />		[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />

Student at 19:38, 28 April 2021

Student — Wed, 28 Apr 2021 19:38:38 GMT

←Older revision		Revision as of 19:38, 28 April 2021
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	'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''		'''The active site of Topo 1 is catalytic and it is the location where the nicking or cutting occurs<ref name="Redinbo" />. The nicking occurs from the trans-esterification of Tyr-723 at a DNA phophodiester bond forming a <scene name='78/781215/04_27_19_active_site_mech/1'>3'-phosphotyrosine covalent enzyme–DNA complex</scene> <ref name="Staker" />. After the DNA is relaxed, the covalent intermediate is reversed when the released 5'-OH of the broken strand reattacks the phosphotyrosine intermediate in a second transesterification reaction<ref name="Staker" />.'''

-	[[Image:Active Site 2.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>	+	[[Image:Active Site 3.jpg]]<ref name ="Stewart">Stewart, L. (1998). A Model for the Mechanism of Human Topoisomerase I. Science, 279(5356), 1534–1541. https://doi.org/10.1126/science.279.5356.1534</ref>

	[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />		[[Image:DNA and Tyrosine.jpg]]<ref name="Stewart" />

Student at 18:51, 28 April 2021

Student — Wed, 28 Apr 2021 18:51:00 GMT

←Older revision		Revision as of 18:51, 28 April 2021
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	== Structure ==		== Structure ==
-	'''Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The <scene name='78/781215/04_27_structure_cooh/1'>COOH-terminal</scene> domain is made up of residues 713 to 765 and contains the important amino ~~aside~~ <scene name='78/781215/04_27_structure_cooh_with_k/1'>Tyrosine 723</scene><ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. Residues 636 to 712 form the <scene name='78/781215/04_27_structure_linker/1'>Linker domain</scene> and they contribute to the enzyme catalytic activity but are not required<ref name="Redinbo" />. The core is divided into 3 subdomains: <scene name='78/781215/04_27_structure_core_sd1/1'>Core Sudomain 1</scene>[215-232 & 320-433], <scene name='78/781215/04_27_structure_core_sd2/1'>Core Subdomain 2</scene>[233-319], and <scene name='78/781215/04_27_structure_core_sd3/1'>Core Subdomain 3</scene>[434-635]<ref name="Redinbo"/>. The <scene name='78/781215/04_27_structure_core_cooh/1'>core and the COOH-terminal domains</scene> are very important for the catalytic activity<ref name="Redinbo" />.'''	+	'''Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The <scene name='78/781215/04_27_structure_cooh/1'>COOH-terminal</scene> domain is made up of residues 713 to 765 and contains the important amino acid <scene name='78/781215/04_27_structure_cooh_with_k/1'>Tyrosine 723</scene><ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. Residues 636 to 712 form the <scene name='78/781215/04_27_structure_linker/1'>Linker domain</scene> and they contribute to the enzyme catalytic activity but are not required<ref name="Redinbo" />. The core is divided into 3 subdomains: <scene name='78/781215/04_27_structure_core_sd1/1'>Core Sudomain 1</scene>[215-232 & 320-433], <scene name='78/781215/04_27_structure_core_sd2/1'>Core Subdomain 2</scene>[233-319], and <scene name='78/781215/04_27_structure_core_sd3/1'>Core Subdomain 3</scene>[434-635]<ref name="Redinbo"/>. The <scene name='78/781215/04_27_structure_core_cooh/1'>core and the COOH-terminal domains</scene> are very important for the catalytic activity<ref name="Redinbo" />.'''
	[[Image:Color Key.jpg]]		[[Image:Color Key.jpg]]
	== Active Site & Mechanism Of Action==		== Active Site & Mechanism Of Action==

Student at 12:22, 28 April 2021

Student — Wed, 28 Apr 2021 12:22:36 GMT

←Older revision		Revision as of 12:22, 28 April 2021
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	== Relevance ==		== Relevance ==
-	'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the <scene name='78/781215/04_28_revelance_cpt_bind/1'>topo I</scene> reaction <ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''	+	'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the <scene name='78/781215/04_28_revelance_cpt_bind/1'>topo I</scene> reaction <ref name="Redinbo" />. CPT enhances DNA breakage at sites with a guanine base at the +1 position on the DNA strand that is being cut<ref name="Redinbo" />. This is immediately downstream of the site that is being cleaved<ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''
	[[Image:CPT and Enzyme.jpg]] <ref name="Redinbo" />		[[Image:CPT and Enzyme.jpg]] <ref name="Redinbo" />

Student at 12:19, 28 April 2021

Student — Wed, 28 Apr 2021 12:19:42 GMT

←Older revision		Revision as of 12:19, 28 April 2021
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	== Relevance ==		== Relevance ==
-	'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the topo I reaction <ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''	+	'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the <scene name='78/781215/04_28_revelance_cpt_bind/1'>topo I</scene> reaction <ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''
	[[Image:CPT and Enzyme.jpg]] <ref name="Redinbo" />		[[Image:CPT and Enzyme.jpg]] <ref name="Redinbo" />

Student at 12:08, 28 April 2021

Student — Wed, 28 Apr 2021 12:08:29 GMT

←Older revision		Revision as of 12:08, 28 April 2021
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	== Relevance ==		== Relevance ==
	'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the topo I reaction <ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''		'''Many anticancer drugs target topo 1 enzymes. This enzyme is the target of camptothecin (CPT) family of anticancer drugs<ref name="Redinbo" />. These drugs work by increasing the duration of the nicked intermediate in the topo I reaction <ref name="Redinbo" />. The stabilized intermediates prevent transcription and replication to continue in the cancer cells<ref name="Redinbo" />. This eventually leads to DNA damage and cell death<ref name="Redinbo" />.'''
		+	[[Image:CPT and Enzyme.jpg]] <ref name="Redinbo" />

	== Mutations ==		== Mutations ==

Student at 06:16, 28 April 2021

Student — Wed, 28 Apr 2021 06:16:39 GMT

←Older revision		Revision as of 06:16, 28 April 2021
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	== Mutations ==		== Mutations ==
-	'''A mutation at amino acid <scene name='78/781215/~~04_27_19_mutation~~/1'>Lysine</scene> 532 to Alanine almost abolishes enzyme activity<ref name="Interthal">DOI 10.1074/jbc.M309959200</ref>. The location of Lys 532 to the scissile phosphate and other active site amino acids could be the reason why a mutation of this amino acid abolishes the enzyme activity<ref name="Interthal" />.	+	'''A mutation at amino acid <scene name='78/781215/04_27_19_mutation_1/1'>Lysine</scene> 532 to Alanine almost abolishes enzyme activity<ref name="Interthal">DOI 10.1074/jbc.M309959200</ref>. The location of Lys 532 to the scissile phosphate and other active site amino acids could be the reason why a mutation of this amino acid abolishes the enzyme activity<ref name="Interthal" />.

	[[Image:Screen_Shot_2021-04-27_at_7.28.18_PM.jpg]]'''		[[Image:Screen_Shot_2021-04-27_at_7.28.18_PM.jpg]]'''

Student at 06:08, 28 April 2021

Student — Wed, 28 Apr 2021 06:08:44 GMT

←Older revision		Revision as of 06:08, 28 April 2021
Line 23:		Line 23:

	== Mutations ==		== Mutations ==
-	'''A mutation at amino acid <scene name='78/781215/~~02_24_21_lys_532_residue~~/1'>Lysine</scene> 532 to Alanine almost abolishes enzyme activity<ref name="Interthal">DOI 10.1074/jbc.M309959200</ref>. The location of Lys 532 to the scissile phosphate and other active site amino acids could be the reason why a mutation of this amino acid abolishes the enzyme activity<ref name="Interthal" />.	+	'''A mutation at amino acid <scene name='78/781215/04_27_19_mutation/1'>Lysine</scene> 532 to Alanine almost abolishes enzyme activity<ref name="Interthal">DOI 10.1074/jbc.M309959200</ref>. The location of Lys 532 to the scissile phosphate and other active site amino acids could be the reason why a mutation of this amino acid abolishes the enzyme activity<ref name="Interthal" />.

	[[Image:Screen_Shot_2021-04-27_at_7.28.18_PM.jpg]]'''		[[Image:Screen_Shot_2021-04-27_at_7.28.18_PM.jpg]]'''

Student at 05:57, 28 April 2021

Student — Wed, 28 Apr 2021 05:57:39 GMT

←Older revision		Revision as of 05:57, 28 April 2021
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	'''Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The <scene name='78/781215/04_27_structure_cooh/1'>COOH-terminal</scene> domain is made up of residues 713 to 765 and contains the important amino aside <scene name='78/781215/04_27_structure_cooh_with_k/1'>Tyrosine 723</scene><ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. Residues 636 to 712 form the <scene name='78/781215/04_27_structure_linker/1'>Linker domain</scene> and they contribute to the enzyme catalytic activity but are not required<ref name="Redinbo" />. The core is divided into 3 subdomains: <scene name='78/781215/04_27_structure_core_sd1/1'>Core Sudomain 1</scene>[215-232 & 320-433], <scene name='78/781215/04_27_structure_core_sd2/1'>Core Subdomain 2</scene>[233-319], and <scene name='78/781215/04_27_structure_core_sd3/1'>Core Subdomain 3</scene>[434-635]<ref name="Redinbo"/>. The <scene name='78/781215/04_27_structure_core_cooh/1'>core and the COOH-terminal domains</scene> are very important for the catalytic activity<ref name="Redinbo" />.'''		'''Human topo 1 is composed of 765 amino acids <ref name="Redinbo" />. The enzyme consist of 4 regions which are the NH2-terminal, core, linker, and COOH-terminal domains<ref name="Redinbo" />. The NH2-terminal is approximately 210 residues long, it is highly charged, disordered, and contains few hydrophobic amino acids<ref name="Redinbo" />. The <scene name='78/781215/04_27_structure_cooh/1'>COOH-terminal</scene> domain is made up of residues 713 to 765 and contains the important amino aside <scene name='78/781215/04_27_structure_cooh_with_k/1'>Tyrosine 723</scene><ref name="Redinbo"/>. The location of the active site is at this amino acid<ref name="Redinbo" />. Residues 636 to 712 form the <scene name='78/781215/04_27_structure_linker/1'>Linker domain</scene> and they contribute to the enzyme catalytic activity but are not required<ref name="Redinbo" />. The core is divided into 3 subdomains: <scene name='78/781215/04_27_structure_core_sd1/1'>Core Sudomain 1</scene>[215-232 & 320-433], <scene name='78/781215/04_27_structure_core_sd2/1'>Core Subdomain 2</scene>[233-319], and <scene name='78/781215/04_27_structure_core_sd3/1'>Core Subdomain 3</scene>[434-635]<ref name="Redinbo"/>. The <scene name='78/781215/04_27_structure_core_cooh/1'>core and the COOH-terminal domains</scene> are very important for the catalytic activity<ref name="Redinbo" />.'''
	[[Image:Color Key.jpg]]		[[Image:Color Key.jpg]]
-	== Active Site ==	+	== Active Site & Mechanism Of Action==
	'''Topo 1 reduces stress in DNA by causing a transient single strand nick in the the DNA helix<ref name="Staker" />. This nick enables the cut to rotate around its intact complement, thus eliminating proximal supercoils<ref name="Staker" />.'''		'''Topo 1 reduces stress in DNA by causing a transient single strand nick in the the DNA helix<ref name="Staker" />. This nick enables the cut to rotate around its intact complement, thus eliminating proximal supercoils<ref name="Staker" />.'''