Triose Phosphate Isomerase Structure & Mechanism - Revision history

Alexander Berchansky at 12:51, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:51:41 GMT

←Older revision		Revision as of 12:51, 8 September 2022
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	<StructureSection load='1hti' size='300' side='right' scene='' caption='Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]]'>		<StructureSection load='1hti' size='300' side='right' scene='' caption='Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]]'>

-	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]<br />	+	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
		+	<br />

	===General Information===		===General Information===

Alexander Berchansky at 12:51, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:51:24 GMT

←Older revision		Revision as of 12:51, 8 September 2022
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	<StructureSection load='1hti' size='300' side='right' scene='' caption='Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]]'>		<StructureSection load='1hti' size='300' side='right' scene='' caption='Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]]'>

-	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]	+	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]<br />

-	{{Clear}}
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

Alexander Berchansky at 12:50, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:50:52 GMT

←Older revision		Revision as of 12:50, 8 September 2022
Line 2:		Line 2:

	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]		[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
		+
	{{Clear}}		{{Clear}}
	===General Information===		===General Information===

Alexander Berchansky at 12:50, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:50:20 GMT

←Older revision		Revision as of 12:50, 8 September 2022
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	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]		[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
-		+	{{Clear}}
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

Alexander Berchansky at 12:49, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:49:50 GMT

←Older revision		Revision as of 12:49, 8 September 2022
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	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]		[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
		+
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

Alexander Berchansky at 12:49, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:49:29 GMT

←Older revision		Revision as of 12:49, 8 September 2022
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	<scene name='Christian_Krenk_Sandbox/Active_site/1'> Glu 165 acts as the base and grabs the C2 proton on glyceraldehyde-3-phosphate, while His 95 is H-bonded to the carbonyl oxygen and acts as the acid by protonating carbonyl oxygen.</scene> The enediol intermediate is negatively charged, but is somewhat <scene name='Christian_Krenk_Sandbox/Lysine/1'>stabilized by the positively charged side chain of Lys 12.</scene> <ref name= "lodi">PMID:8130193</ref> Mutation of Lys 12 to Arg increases Km by a factor of 22 and decreases Vmax by a factor of 180.<ref name="lodi" /> To convert the enediol intermediate to DHAP, C1 is protonated by Glu 165, with His 95 removing a proton from C2’s OH group. As a result, the catalytic groups are back to their original states, and catalysis is complete. With GAP as a substrate, Km for the reaction is .34 mM and Vmax is 7200 units/mg protein at 25 degrees C and pH 7.5.<ref name= "dab" />		<scene name='Christian_Krenk_Sandbox/Active_site/1'> Glu 165 acts as the base and grabs the C2 proton on glyceraldehyde-3-phosphate, while His 95 is H-bonded to the carbonyl oxygen and acts as the acid by protonating carbonyl oxygen.</scene> The enediol intermediate is negatively charged, but is somewhat <scene name='Christian_Krenk_Sandbox/Lysine/1'>stabilized by the positively charged side chain of Lys 12.</scene> <ref name= "lodi">PMID:8130193</ref> Mutation of Lys 12 to Arg increases Km by a factor of 22 and decreases Vmax by a factor of 180.<ref name="lodi" /> To convert the enediol intermediate to DHAP, C1 is protonated by Glu 165, with His 95 removing a proton from C2’s OH group. As a result, the catalytic groups are back to their original states, and catalysis is complete. With GAP as a substrate, Km for the reaction is .34 mM and Vmax is 7200 units/mg protein at 25 degrees C and pH 7.5.<ref name= "dab" />

-	[[Image:ckrenkmechanism.jpg\|left\|thumb\|~~650px~~\| '''Mechanism of Triose phosphate isomerase'''. Created by Christian Krenk using Spartan 08.]]	+	[[Image:ckrenkmechanism.jpg\|left\|thumb\|400px\| '''Mechanism of Triose phosphate isomerase'''. Created by Christian Krenk using Spartan 08.]]

	An interesting part of the enzyme is the <scene name='Christian_Krenk_Sandbox/Flexible_loop/1'>flexible loop</scene> that stabilizes the enediol-like transition state. The flexible loop (residues 167-176)<ref>PMID:2204418</ref> closes over the active site like a hinged lid when substrate is bound, thus preventing phosphate from leaving. A four-residue segment of the loop H-bonds with the phosphate group of the substrate.<ref name="book" /> Without the loop, the enediol intermediate would eliminate phosphate, with the end products being inorganic phosphate and toxic methylglyoxal.<ref name="book" />		An interesting part of the enzyme is the <scene name='Christian_Krenk_Sandbox/Flexible_loop/1'>flexible loop</scene> that stabilizes the enediol-like transition state. The flexible loop (residues 167-176)<ref>PMID:2204418</ref> closes over the active site like a hinged lid when substrate is bound, thus preventing phosphate from leaving. A four-residue segment of the loop H-bonds with the phosphate group of the substrate.<ref name="book" /> Without the loop, the enediol intermediate would eliminate phosphate, with the end products being inorganic phosphate and toxic methylglyoxal.<ref name="book" />

Alexander Berchansky at 12:48, 8 September 2022

Alexander Berchansky — Thu, 08 Sep 2022 12:48:30 GMT

←Older revision		Revision as of 12:48, 8 September 2022
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		+	<StructureSection load='1hti' size='300' side='right' scene='' caption='Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]]'>
		+
	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]		[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
	===General Information===		===General Information===
Line 15:		Line 17:

	An interesting part of the enzyme is the <scene name='Christian_Krenk_Sandbox/Flexible_loop/1'>flexible loop</scene> that stabilizes the enediol-like transition state. The flexible loop (residues 167-176)<ref>PMID:2204418</ref> closes over the active site like a hinged lid when substrate is bound, thus preventing phosphate from leaving. A four-residue segment of the loop H-bonds with the phosphate group of the substrate.<ref name="book" /> Without the loop, the enediol intermediate would eliminate phosphate, with the end products being inorganic phosphate and toxic methylglyoxal.<ref name="book" />		An interesting part of the enzyme is the <scene name='Christian_Krenk_Sandbox/Flexible_loop/1'>flexible loop</scene> that stabilizes the enediol-like transition state. The flexible loop (residues 167-176)<ref>PMID:2204418</ref> closes over the active site like a hinged lid when substrate is bound, thus preventing phosphate from leaving. A four-residue segment of the loop H-bonds with the phosphate group of the substrate.<ref name="book" /> Without the loop, the enediol intermediate would eliminate phosphate, with the end products being inorganic phosphate and toxic methylglyoxal.<ref name="book" />
-
-
-
-	{{STRUCTURE_1wyi\| PDB=1wyi \| SIZE=400\| SCENE= \|right\|CAPTION=Human triosephosphate isomerase, [[1wyi]] }}
-
-
-	{{STRUCTURE_1hti\| PDB=1hti \| SIZE=400\| SCENE= \|right\|CAPTION=Human triosephosphate isomerase complex with phosphoglycolic acid [[1hti]] }}

	==3D structures of triose phosphate isomerase==		==3D structures of triose phosphate isomerase==
Line 30:		Line 25:
	For additional information, see: [[Carbohydrate Metabolism]]		For additional information, see: [[Carbohydrate Metabolism]]
	<br />		<br />
-		+	</StructureSection>
	===References===		===References===

	<references/>		<references/>
	7. Wierenga RK, Kapetaniou EG, Venkatesan R. Triosephosphate isomerase: a highly evolved biocatalyst. Cellular and Molecular Life Sciences. 2010 August 7 67:3961-3982. PMID: 20694739 <ref>PMID:20694739</ref>		7. Wierenga RK, Kapetaniou EG, Venkatesan R. Triosephosphate isomerase: a highly evolved biocatalyst. Cellular and Molecular Life Sciences. 2010 August 7 67:3961-3982. PMID: 20694739 <ref>PMID:20694739</ref>

Jane S. Richardson at 17:31, 5 June 2012

Jane S. Richardson — Tue, 05 Jun 2012 17:31:12 GMT

←Older revision		Revision as of 17:31, 5 June 2012
Line 1:		Line 1:
-	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|~~280px~~\|Ribbon drawing for one ~~subunit~~ of the "TIM barrel" fold]]	+	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|300px\|Ribbon drawing for one chain of the "TIM barrel" fold]]
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

Jane S. Richardson at 17:28, 5 June 2012

Jane S. Richardson — Tue, 05 Jun 2012 17:28:45 GMT

←Older revision		Revision as of 17:28, 5 June 2012
Line 1:		Line 1:
-	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|~~240px~~\|Ribbon drawing for one subunit of the "TIM barrel" fold]]	+	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|280px\|Ribbon drawing for one subunit of the "TIM barrel" fold]]
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

Jane S. Richardson: added image

Jane S. Richardson — Tue, 05 Jun 2012 17:28:15 GMT

added image

←Older revision		Revision as of 17:28, 5 June 2012
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		+	[[Image:TriosePhosphateIsomerase_Ribbon_pastel_photo_small.jpg\|thumb\|left\|240px\|Ribbon drawing for one subunit of the "TIM barrel" fold]]
	===General Information===		===General Information===
	Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.		Triose phosphate isomerase (TIM)<ref>PMID:16511037</ref><ref>PMID:8061610</ref> (PDB [[1wyi]] and [[1hti]]) is a crucial enzyme in the glycolytic pathway. <scene name='Christian_Krenk_Sandbox/Nc_rainbow/1'>TIM</scene> reversibly converts the aldose Glyceraldehyde-3-phosphate (GAP) to the ketose Dihydroxyacetone phosphate (DHAP). The interconversion proceeds by an enediol intermediate. Triose phosphate isomerase is not directly regulated, but the enzyme two steps before it in the glycolytic pathway, phosphofructokinase, is a heavily regulated, irreversible enzyme.

	===Structural Characteristics===		===Structural Characteristics===
-	The secondary structure consists of 14 alpha helices and 8 beta sheets per monomer, making it fall in the SCOP category of alpha and beta proteins. The tertiary structure is a <scene name='Christian_Krenk_Sandbox/Alpha_beta_barrel/2'>alpha-beta barrel.</scene>	+	The secondary structure consists of 14 alpha helices and 8 beta sheets per monomer, making it fall in the SCOP category of alpha and beta proteins. The tertiary structure is a <scene name='Christian_Krenk_Sandbox/Alpha_beta_barrel/2'>alpha-beta barrel</scene>, and it is the prototypical example of the "TIM barrel" fold (see ribbon drawing).
	The quaternary structure is a homodimer. The molecular weight of the enzyme is estimated at 57,400 Da.<ref name= "dab">PMID:752201</ref>		The quaternary structure is a homodimer. The molecular weight of the enzyme is estimated at 57,400 Da.<ref name= "dab">PMID:752201</ref>