Isopropylmalate dehydrogenase

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<StructureSection load='4f7i' size='450' side='right' caption='3-isopropylmalate dehydrogenase complex with 3-isopropylmalate, glycerol, NAD, PMSF, Mn+2 and K+ ions (purple) (PDB entry [[4f7i]])' scene='49/490899/Cv/1'>
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<StructureSection load='' size='350' side='right' caption='3-isopropylmalate dehydrogenase complex with 3-isopropylmalate, glycerol, NAD, PMSF, Mn+2 and K+ ions (purple) (PDB entry [[4f7i]])' scene='49/490899/Cv/1'>
== Function ==
== Function ==
'''3-Isopropylmalate dehydrogenase''' (IMDH) catalyzes the oxidative decarboxylation of 3-isopropylmalate (3IPM) to 2-oxo-4-methylvalerate. This reaction is a step in the biosynthesis of leucine in bacteria and fungi. IMDH uses [[NAD]] as a cofactor. IMDH is a bifunctional enzyme that catalyzes dehydrogenation and decarboxylation in the presence of NAD and a divalent cation<ref>PMID:17979826</ref>.
'''3-Isopropylmalate dehydrogenase''' (IMDH) catalyzes the oxidative decarboxylation of 3-isopropylmalate (3IPM) to 2-oxo-4-methylvalerate. This reaction is a step in the biosynthesis of leucine in bacteria and fungi. IMDH uses [[NAD]] as a cofactor. IMDH is a bifunctional enzyme that catalyzes dehydrogenation and decarboxylation in the presence of NAD and a divalent cation<ref>PMID:17979826</ref>.
== Structural highlights ==
== Structural highlights ==
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<scene name='49/490899/Cv/2'>3-isopropylmalate dehydrogenase complex with 3-isopropylmalate, glycerol, NAD, PMSF, Mn+2 and K- ions</scene>.
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<scene name='49/490899/Cv/11'>3-isopropylmalate dehydrogenase complex with 3-isopropylmalate, glycerol, NAD, PMSF, Mn+2 and K- ions</scene>.
IMDH active site containing the <scene name='49/490899/Cv/9'>NAD cofactor is located between 2 subunits</scene> and contains the substrate and Mn+2 and K- ions<ref>PMID:25211160</ref>. Water molecules shown as red spheres.
IMDH active site containing the <scene name='49/490899/Cv/9'>NAD cofactor is located between 2 subunits</scene> and contains the substrate and Mn+2 and K- ions<ref>PMID:25211160</ref>. Water molecules shown as red spheres.
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<scene name='49/490899/Cv/4'>MN coordination site</scene>.
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<scene name='49/490899/Cv/12'>MN coordination site</scene>.
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<scene name='49/490899/Cv/6'>K coordination site</scene>.
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<scene name='49/490899/Cv/13'>K coordination site</scene>.
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<scene name='49/490899/Cv/5'>3-isopropylmalate binding site</scene>.
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<scene name='49/490899/Cv/14'>3-isopropylmalate binding site</scene>.
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<scene name='49/490899/Cv/10'>Whole IMDH active site</scene>.
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<scene name='49/490899/Cv/15'>Whole IMDH active site</scene>.
</StructureSection>
</StructureSection>
==3D structures of isopropylmalate dehydrogenase==
==3D structures of isopropylmalate dehydrogenase==
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**[[3h5e]], [[3h5h]], [[3h5j]] - MtIMDH small subunit<br />
**[[3h5e]], [[3h5h]], [[3h5j]] - MtIMDH small subunit<br />
**[[2hcu]] – IMDH small subunit – ''Streptococcus mutans''<br />
**[[2hcu]] – IMDH small subunit – ''Streptococcus mutans''<br />
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**[[3q3w]], [[3udo]] - IMDH small subunit – ''Campylobacter jejuni''<br />
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**[[3q3w]], [[3udu]] - IMDH small subunit – ''Campylobacter jejuni''<br />
**[[3r8w]] - AtIMDH – ''Arabidopsis thaliana''<br />
**[[3r8w]] - AtIMDH – ''Arabidopsis thaliana''<br />
**[[3u1h]] - IMDH – ''Bacillus''<br />
**[[3u1h]] - IMDH – ''Bacillus''<br />
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**[[1a05]] – IMDH + 3IPM + Mg - ''Acidithiobacillus ferrooxidans''<br />
**[[1a05]] – IMDH + 3IPM + Mg - ''Acidithiobacillus ferrooxidans''<br />
**[[3vkz]], [[3vl2]], [[3vl3]], [[3vl4]], [[3vl6]], [[3vl7]] - SoIMDH + 3IPM + Ca <br />
**[[3vkz]], [[3vl2]], [[3vl3]], [[3vl4]], [[3vl6]], [[3vl7]] - SoIMDH + 3IPM + Ca <br />
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**[[3vmj]], [[3wzw]] - SoIMDH + 3IPM + Mg<br />
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**[[3vmj]], [[3wzw]], [[3wzv]] - SoIMDH + 3IPM + Mg<br />
**[[3wzy]], [[3wzx]] - SoIMDH (mutant) + 3IPM + Mg<br />
**[[3wzy]], [[3wzx]] - SoIMDH (mutant) + 3IPM + Mg<br />
**[[3vmk]] - SoIMDH + 3IPM + Mg <br />
**[[3vmk]] - SoIMDH + 3IPM + Mg <br />
**[[4y1p]] - IMDH + 3IPM + Mg – ''Sulfolobus acidarius''<br />
**[[4y1p]] - IMDH + 3IPM + Mg – ''Sulfolobus acidarius''<br />
**[[5j32]] - AtIMDH + 3IPM + Mg<br />
**[[5j32]] - AtIMDH + 3IPM + Mg<br />
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**[[6xxy]] - IMDH (mutant) + NAD + isobutenyl oxalylhydroxamate – ''Haemophilus influenzae''<BR />
}}
}}

Current revision

3-isopropylmalate dehydrogenase complex with 3-isopropylmalate, glycerol, NAD, PMSF, Mn+2 and K+ ions (purple) (PDB entry 4f7i)

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3D structures of isopropylmalate dehydrogenase

Updated on 30-August-2020

References

  1. Martignon S, Rossi F, Rizzi M. Expression, purification and characterisation of Haemophilus influenzae 3-isopropylmalate dehydrogenase (LeuB). Protein Pept Lett. 2007;14(8):822-7. PMID:17979826
  2. Pallo A, Olah J, Graczer E, Merli A, Zavodszky P, Weiss MS, Vas M. Structural and energetic basis of isopropylmalate dehydrogenase enzyme catalysis. FEBS J. 2014 Sep 11. doi: 10.1111/febs.13044. PMID:25211160 doi:http://dx.doi.org/10.1111/febs.13044

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Michal Harel, Alexander Berchansky, Joel L. Sussman

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