2-isopropylmalate synthase - Revision history

Michal Harel at 09:26, 19 May 2024

Michal Harel — Sun, 19 May 2024 09:26:58 GMT

←Older revision		Revision as of 09:26, 19 May 2024
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	<StructureSection load='' size='400' side='right' caption='2-isopropylmalate synthase complex with leucine, glycerol and Zn+2 ion (grey) (PDB code [[3fig]])' scene='74/748866/Cv/1'>		<StructureSection load='' size='400' side='right' caption='2-isopropylmalate synthase complex with leucine, glycerol and Zn+2 ion (grey) (PDB code [[3fig]])' scene='74/748866/Cv/1'>

-		+	__TOC__
	== Function ==		== Function ==
	'''2-isopropylmalate synthase''' (LeuA) or '''α-isopropylmalate synthase''' catalyzes the reversible conversion of 3-methyl-2-oxobutanoate and acetyl-CoA to 2-isopropylmalate. LeuA participates in the biosynthesis of leucine and pyruvate metabolism<ref>PMID:16846242</ref>. It is involved in the second step of the leucine biosynthetic pathway, catalyzing the formation of 2-isopropylmalate from acetyl-CoA and α-ketoisovalerate.		'''2-isopropylmalate synthase''' (LeuA) or '''α-isopropylmalate synthase''' catalyzes the reversible conversion of 3-methyl-2-oxobutanoate and acetyl-CoA to 2-isopropylmalate. LeuA participates in the biosynthesis of leucine and pyruvate metabolism<ref>PMID:16846242</ref>. It is involved in the second step of the leucine biosynthetic pathway, catalyzing the formation of 2-isopropylmalate from acetyl-CoA and α-ketoisovalerate.

Joel L. Sussman at 08:19, 15 June 2023

Joel L. Sussman — Thu, 15 Jun 2023 08:19:09 GMT

←Older revision		Revision as of 08:19, 15 June 2023
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	== Function ==		== Function ==
-	'''2-isopropylmalate synthase''' (LeuA) or '''α-isopropylmalate synthase''' catalyzes the reversible conversion of 3-methyl-2-oxobutanoate and acetyl-CoA to 2-isopropylmalate. LeuA participates in the biosynthesis of leucine and pyruvate metabolism<ref>PMID:16846242</ref>.	+	'''2-isopropylmalate synthase''' (LeuA) or '''α-isopropylmalate synthase''' catalyzes the reversible conversion of 3-methyl-2-oxobutanoate and acetyl-CoA to 2-isopropylmalate. LeuA participates in the biosynthesis of leucine and pyruvate metabolism<ref>PMID:16846242</ref>. It is involved in the second step of the leucine biosynthetic pathway, catalyzing the formation of 2-isopropylmalate from acetyl-CoA and α-ketoisovalerate.
		+
		+	The leucine biosynthetic pathway is found in bacteria, fungi, plants, and some archaea. It allows these organisms to synthesize leucine, an essential amino acid that cannot be produced by animals and must be obtained through the diet.
		+
		+	The reaction catalyzed by 2-isopropylmalate synthase involves condensing acetyl-CoA with α-ketoisovalerate, resulting in the formation of 2-isopropylmalate. This reaction is a key step in the conversion of α-ketoisovalerate into α-isopropylmalate, which is subsequently converted to leucine through a series of enzymatic reactions.
		+
		+	2-Isopropylmalate synthase is a pyrocatechol-4,5-dioxygenase-like enzyme and requires divalent metal ions, such as manganese or magnesium, as cofactors for its activity. The enzyme is typically composed of multiple subunits and can vary in structure and organization among different organisms.
		+
		+	Understanding the structure and function of 2-isopropylmalate synthase is important for studying the biosynthesis of leucine and related amino acids. It is also a potential target for the development of antimicrobial agents, as the leucine biosynthetic pathway is unique to microorganisms and absent in animals, making it an attractive target for selective inhibition.

	== Structural highlights ==		== Structural highlights ==

Alexander Berchansky at 11:49, 2 December 2020

Alexander Berchansky — Wed, 02 Dec 2020 11:49:10 GMT

←Older revision		Revision as of 11:49, 2 December 2020
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	== Structural highlights ==		== Structural highlights ==
-	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. Water molecules are shown as red spheres<scene name='74/748866/Cv/7'>Leucine binding site</scene>.	+	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. Water molecules are shown as red spheres. <scene name='74/748866/Cv/7'>Leucine binding site</scene>.

	==3D structures of 2-isopropylmalate synthase==		==3D structures of 2-isopropylmalate synthase==

Alexander Berchansky at 11:48, 2 December 2020

Alexander Berchansky — Wed, 02 Dec 2020 11:48:23 GMT

←Older revision		Revision as of 11:48, 2 December 2020
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-	<StructureSection load='' size='~~450~~' side='right' caption='2-isopropylmalate synthase complex with leucine, glycerol and Zn+2 ion (grey) (PDB code [[3fig]])' scene='74/748866/Cv/1'>	+	<StructureSection load='' size='400' side='right' caption='2-isopropylmalate synthase complex with leucine, glycerol and Zn+2 ion (grey) (PDB code [[3fig]])' scene='74/748866/Cv/1'>

Alexander Berchansky at 14:10, 23 October 2019

Alexander Berchansky — Wed, 23 Oct 2019 14:10:14 GMT

←Older revision		Revision as of 14:10, 23 October 2019
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	== Structural highlights ==		== Structural highlights ==
-	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. <scene name='74/748866/Cv/7'>Leucine binding site</scene>.	+	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. Water molecules are shown as red spheres<scene name='74/748866/Cv/7'>Leucine binding site</scene>.

	==3D structures of 2-isopropylmalate synthase==		==3D structures of 2-isopropylmalate synthase==

Michal Harel at 09:08, 20 February 2019

Michal Harel — Wed, 20 Feb 2019 09:08:31 GMT

←Older revision		Revision as of 09:08, 20 February 2019
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	</StructureSection>		</StructureSection>
-	==3D structures of 2-isopropylmalate synthase==

-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-	*2-isopropylmalate synthase
-
-	**[[4ov4]] – LbLeuA + ketoisovalerate + Zn – ''Leptospira biflexa''<br />
-	**[[4ov9]] – LbLeuA + 2-isopropylmalate + Zn <br />
-	**[[3hps]] – MtLeuA + isoketocaproate + leucine + Zn - ''Mycobacterium tuberculosis'' <br />
-	**[[3hpz]] – MtLeuA + bromopyruvate + Zn<br />
-	**[[3hq1]] – MtLeuA + citrate + Zn<br />
-	**[[3fig]] – MtLeuA (mutant) + leucine + Zn<br />
-	**[[1sr9]] – MtLeuA + ketovaline + Zn<br />
-	**[[3eeg]] – LeuA – ''Cytophaga hutchinsonii''<br />
-
-	*2-isopropylmalate synthase catalytic domain
-
-	**[[3rmj]] – LeuA + Mg + Mn – ''Neisseria meningitidis''<br />
-	**[[3u6w]] – MtLeuA + ketovaline + Mn <br />
-	**[[3hpx]] – MtLeuA (mutant) + Ni<br />
-
-	*2-isopropylmalate synthase regulatory domain
-
-	**[[3f6h]], [[3f6g]] – EcLeuA + isoleucine + Zn – ''Escherichia coli''<br />
-
-	*2-isopropylmalate synthase N-terminal domain
-
-	**[[3ewb]] – LeuA – ''Listeria Monocytogenes''<br />
-	}}
	== References ==		== References ==
	<references/>		<references/>
	[[Category: Topic Page]]		[[Category: Topic Page]]

Michal Harel at 09:04, 20 February 2019

Michal Harel — Wed, 20 Feb 2019 09:04:10 GMT

←Older revision		Revision as of 09:04, 20 February 2019
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	== Structural highlights ==		== Structural highlights ==
	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. <scene name='74/748866/Cv/7'>Leucine binding site</scene>.		<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. <scene name='74/748866/Cv/7'>Leucine binding site</scene>.
		+
		+	==3D structures of 2-isopropylmalate synthase==
		+	[[2-isopropylmalate synthase 3D structures]]
		+
	</StructureSection>		</StructureSection>
	==3D structures of 2-isopropylmalate synthase==		==3D structures of 2-isopropylmalate synthase==

Alexander Berchansky at 11:22, 16 December 2018

Alexander Berchansky — Sun, 16 Dec 2018 11:22:46 GMT

←Older revision		Revision as of 11:22, 16 December 2018
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	== Structural highlights ==		== Structural highlights ==
-	<scene name='74/748866/Cv/2'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/3'>Zn+2 ion</scene><ref>PMID:15159544</ref>. <scene name='74/748866/Cv/4'>Leucine binding site</scene>.	+	<scene name='74/748866/Cv/5'>Domain organization of LeuA</scene>. LeuA structure is composed of 2 major domains - the catalytic N-terminal which shows a TIM barrel conformation and the regulatory C-terminal. The 2 domains are separated by subdomains I and II and a short flexible hinge region between the 2 subdomains. The catalytic domain binds the substrate and the <scene name='74/748866/Cv/6'>Zn+2 ion</scene><ref>PMID:15159544</ref>. <scene name='74/748866/Cv/7'>Leucine binding site</scene>.
	</StructureSection>		</StructureSection>
	==3D structures of 2-isopropylmalate synthase==		==3D structures of 2-isopropylmalate synthase==

Michal Harel at 08:13, 1 March 2018

Michal Harel — Thu, 01 Mar 2018 08:13:14 GMT

←Older revision		Revision as of 08:13, 1 March 2018
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	**[[3f6h]], [[3f6g]] – EcLeuA + isoleucine + Zn – ''Escherichia coli''<br />		**[[3f6h]], [[3f6g]] – EcLeuA + isoleucine + Zn – ''Escherichia coli''<br />
		+
		+	*2-isopropylmalate synthase N-terminal domain
		+
		+	**[[3ewb]] – LeuA – ''Listeria Monocytogenes''<br />
	}}		}}
	== References ==		== References ==
	<references/>		<references/>
	[[Category: Topic Page]]		[[Category: Topic Page]]

Michal Harel at 16:40, 18 October 2017

Michal Harel — Wed, 18 Oct 2017 16:40:27 GMT

←Older revision		Revision as of 16:40, 18 October 2017
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	== References ==		== References ==
	<references/>		<references/>
		+	[[Category: Topic Page]]