Isopropylmalate dehydrogenase

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{{STRUCTURE_2ayq| PDB=2ayq | SIZE=400| SCENE= |right|CAPTION=Isopropylmalate dehydrogenase dimer [[2ayq]] }}
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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'>
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== Function ==
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'''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>.
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== Structural highlights ==
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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>.
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'''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.
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==3D structures of isopropylmalate dehydrogenase==
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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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'''3-isopropylmalate dehydrogenase'''
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<scene name='49/490899/Cv/12'>MN 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/14'>3-isopropylmalate binding site</scene>.
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<scene name='49/490899/Cv/15'>Whole IMDH active site</scene>.
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</StructureSection>
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==3D structures of isopropylmalate dehydrogenase==
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[[1ipd]], [[1xaa]], [[1xab]], [[1xac]], [[1xad]], [[1osi]], [[1dpz]], [[1dr0]], [[1dr8]], [[2y3z]] – TtIMDH – ''Thermus thermophilus''<br />
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[1idm]], [[1osj]], [[1wal]], [[1gc8]], [[1gc9]], [[1g2u]] – TtIMDH (mutant) <br />
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{{#tree:id=OrganizedByTopic|openlevels=0|
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[[2ayq]], [[1v53]] – BcIMDH – ''Bacillus coagulans''<br />
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[[1v5b]] – BcIMDH (mutant) <br />
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[[1cm7]] – IMDH – ''Escherichia coli''<br />
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[[1vlc]] – IMDH – ''Thermotoga maritima''<br />
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[[1v7l]] - IMDH – ''Pyrococcus horikoshii''<br />
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[[1w0d]], [[2g4o]] - MtIMDH - ''Mycobacterium tuberculosis''<br />
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[[3h5e]], [[3h5h]], [[3h5j]] - MtIMDH small subunit<br />
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[[2hcu]] – IMDH small subunit – ''Streptococcus mutans''<br />
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[[3q3w]], [[3udo]] - IMDH small subunit – ''Campylobacter jejuni''<br />
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[[3r8w]] - IMDH – ''Arabidopsis thaliana''<br />
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[[3u1h]] - IMDH – ''Bacillus''<br />
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[[3vml]] - SoIMDH – ''Shewanella oneidensis/Shewanella benthica''<br />
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'''IMDH binary complexes'''
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*3-isopropylmalate dehydrogenase
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[[1hex]] – TtIMDH + NAD<BR />
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**[[1ipd]], [[1xaa]], [[1xab]], [[1xac]], [[1xad]], [[1osi]], [[1dpz]], [[1dr0]], [[1dr8]], [[2y3z]] – TtIMDH – ''Thermus thermophilus''<br />
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[[2y40]] - TtIMDH + Mn<br />
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**[[1idm]], [[1osj]], [[1wal]], [[1gc8]], [[1gc9]], [[1g2u]] – TtIMDH (mutant) <br />
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[[1cnz]] – IMDH + Mn – ''Salmonella typhimurium''<br />
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**[[2ayq]], [[1v53]] – BcIMDH – ''Bacillus coagulans''<br />
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[[1wpw]] - IMDH + Mg – ''Sulfolobus tokodaii''<br />
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**[[1v5b]] – BcIMDH (mutant) <br />
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[[2pkp]] - IMDH small subunit + Zn – ''Methanocaldococcus jannaschii''<br />
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**[[1cm7]] – IMDH – ''Escherichia coli''<br />
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[[4iwh]] - IMDH + Mg – ''Burkholderia thailandensis''<br />
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**[[1vlc]] – IMDH – ''Thermotoga maritima''<br />
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**[[1v7l]] - IMDH – ''Pyrococcus horikoshii''<br />
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**[[1w0d]], [[2g4o]] - MtIMDH - ''Mycobacterium tuberculosis''<br />
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**[[3h5e]], [[3h5h]], [[3h5j]] - MtIMDH small subunit<br />
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**[[2hcu]] – IMDH small subunit – ''Streptococcus mutans''<br />
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**[[3q3w]], [[3udu]] - IMDH small subunit – ''Campylobacter jejuni''<br />
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**[[3r8w]] - AtIMDH – ''Arabidopsis thaliana''<br />
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**[[3u1h]] - IMDH – ''Bacillus''<br />
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**[[3vml]] - SoIMDH – ''Shewanella oneidensis/Shewanella benthica''<br />
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'''IMDH ternary complexes'''
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*IMDH binary complexes
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[[2y42]] - TtIMDH + Mn + NAD<BR />
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**[[1hex]] – TtIMDH + NAD<BR />
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[[2ztw]] - TtIMDH + Mg + inhibitor + NAD<BR />
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**[[2y40]] - TtIMDH + Mn<br />
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[[2y41]] - TtIMDH + 3IPM + Mn<br />
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**[[1cnz]] – IMDH + Mn – ''Salmonella typhimurium''<br />
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[[4f7i]] - TtIMDH + Mg + 3IPM + NAD<br />
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**[[1wpw]] - IMDH + Mg – ''Sulfolobus tokodaii''<br />
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[[1a05]] – IMDH + 3IPM + Mg - ''Acidithiobacillus ferrooxidans''<br />
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**[[2pkp]] - IMDH small subunit + Zn – ''Methanocaldococcus jannaschii''<br />
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[[3vkz]], [[3vl2]], [[3vl3]], [[3vl4]], [[3vl6]], [[3vl7]] - SoIMDH + 3IPM + Ca – ''Shewanella oneidensis''<br />
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**[[4iwh]] - BtIMDH + Mg – ''Burkholderia thailandensis''<br />
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[[3vmj]] - SoIMDH + 3IPM + Mg<br />
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**[[4xxv]] - BtIMDH + NAD<br />
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[[3vmk]] - IMDH + 3IPM + Mg – ''Shewanella bethica''
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**[[5j33]] - AtIMDH + NAD<br />
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**[[5j34]] - AtIMDH + Mg<br />
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'''2-isopropylmalate dehydrogenase'''
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*IMDH ternary complexes
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[[3fig]] - MtIMDH (mutant) + Zn
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**[[2y42]] - TtIMDH + Mn + NAD<BR />
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**[[2ztw]] - TtIMDH + Mg + inhibitor + NAD<BR />
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**[[2y41]] - TtIMDH + 3IPM + Mn<br />
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**[[4f7i]] - TtIMDH + Mg + 3IPM + NAD<br />
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**[[4wuo]] - TtIMDH (mutant) + Mn + 3IPM + NAD<br />
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**[[1a05]] – IMDH + 3IPM + Mg - ''Acidithiobacillus ferrooxidans''<br />
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**[[3vkz]], [[3vl2]], [[3vl3]], [[3vl4]], [[3vl6]], [[3vl7]] - SoIMDH + 3IPM + Ca <br />
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**[[3vmj]], [[3wzw]], [[3wzv]] - SoIMDH + 3IPM + Mg<br />
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**[[3wzy]], [[3wzx]] - SoIMDH (mutant) + 3IPM + Mg<br />
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**[[3vmk]] - SoIMDH + 3IPM + Mg <br />
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**[[4y1p]] - IMDH + 3IPM + Mg – ''Sulfolobus acidarius''<br />
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**[[5j32]] - AtIMDH + 3IPM + Mg<br />
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**[[6xxy]] - IMDH (mutant) + NAD + isobutenyl oxalylhydroxamate – ''Haemophilus influenzae''<BR />
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}}
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

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

Drag the structure with the mouse to rotate

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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

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