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==CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE== | |||
<StructureSection load='1a05' size='340' side='right'caption='[[1a05]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1a05]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Acidithiobacillus_ferrooxidans Acidithiobacillus ferrooxidans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A05 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPM:3-ISOPROPYLMALIC+ACID'>IPM</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1a05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a05 OCA], [https://pdbe.org/1a05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a05 RCSB], [https://www.ebi.ac.uk/pdbsum/1a05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a05 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LEU3_ACIFR LEU3_ACIFR] Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate. | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a0/1a05_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a05 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH. | |||
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.,Imada K, Inagaki K, Matsunami H, Kawaguchi H, Tanaka H, Tanaka N, Namba K Structure. 1998 Aug 15;6(8):971-82. PMID:9739088<ref>PMID:9739088</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1a05" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]] | |||
[[ | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acidithiobacillus ferrooxidans]] | [[Category: Acidithiobacillus ferrooxidans]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Imada | [[Category: Imada K]] | ||
[[Category: Inagaki | [[Category: Inagaki K]] | ||
[[Category: Kawaguchi | [[Category: Kawaguchi H]] | ||
[[Category: Matsunami | [[Category: Matsunami H]] | ||
[[Category: Namba | [[Category: Namba K]] | ||
[[Category: Tanaka | [[Category: Tanaka H]] | ||
[[Category: Tanaka | [[Category: Tanaka N]] | ||
Latest revision as of 13:42, 2 August 2023
CRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATECRYSTAL STRUCTURE OF THE COMPLEX OF 3-ISOPROPYLMALATE DEHYDROGENASE FROM THIOBACILLUS FERROOXIDANS WITH 3-ISOPROPYLMALATE
Structural highlights
FunctionLEU3_ACIFR Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH. Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.,Imada K, Inagaki K, Matsunami H, Kawaguchi H, Tanaka H, Tanaka N, Namba K Structure. 1998 Aug 15;6(8):971-82. PMID:9739088[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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