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| | ==THE CRYSTAL STRUCTURE OF THERMUS THERMOPHILUS 3-ISOPROPYLMALATE DEHYDROGENASE MUTATED AT 172TH FROM ALA TO GLY== | | ==THE CRYSTAL STRUCTURE OF THERMUS THERMOPHILUS 3-ISOPROPYLMALATE DEHYDROGENASE MUTATED AT 172TH FROM ALA TO GLY== |
| - | <StructureSection load='1gc9' size='340' side='right' caption='[[1gc9]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='1gc9' size='340' side='right'caption='[[1gc9]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1gc9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thet8 Thet8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GC9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1gc9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GC9 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ipd|1ipd]], [[1osj|1osj]], [[1gc8|1gc8]], [[1dpz|1dpz]], [[1dr0|1dr0]], [[1dr8|1dr8]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LEUB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=300852 THET8])</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=1gc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gc9 OCA], [https://pdbe.org/1gc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gc9 RCSB], [https://www.ebi.ac.uk/pdbsum/1gc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gc9 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-isopropylmalate_dehydrogenase 3-isopropylmalate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.85 1.1.1.85] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gc9 OCA], [http://pdbe.org/1gc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1gc9 RCSB], [http://www.ebi.ac.uk/pdbsum/1gc9 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LEU3_THET8 LEU3_THET8]] 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.[HAMAP-Rule:MF_01033] | + | [https://www.uniprot.org/uniprot/LEU3_THET8 LEU3_THET8] 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.[HAMAP-Rule:MF_01033] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/1gc9_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gc/1gc9_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-isopropylmalate dehydrogenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Thet8]] | + | [[Category: Thermus thermophilus HB8]] |
| - | [[Category: Akanuma, S]] | + | [[Category: Akanuma S]] |
| - | [[Category: Moriyama, H]] | + | [[Category: Moriyama H]] |
| - | [[Category: Oshima, T]] | + | [[Category: Oshima T]] |
| - | [[Category: Qu, C]] | + | [[Category: Qu C]] |
| - | [[Category: Tanaka, N]] | + | [[Category: Tanaka N]] |
| - | [[Category: Decarboxylation]]
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| - | [[Category: Dehydrogenation]]
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| - | [[Category: Imdh]]
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| - | [[Category: Ipmdh]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Thermostability]]
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| Structural highlights
Function
LEU3_THET8 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.[HAMAP-Rule:MF_01033]
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 PubMed
The relationship between the structure and the thermostability of the 3-isopropylmalate dehydrogenase from Thermus thermophilus was studied by site-directed mutation of a single Ala residue located at the domain interface. The crystal structures of three mutant enzymes, replacing Ala172 with Gly, Val and Phe, were successfully determined at 2.3, 2.2 and 2.5 A resolution, respectively. Substitution of Ala172 by relatively 'short' residues (Gly, Val or Ile) enlarges or narrows the cavity in the vicinity of the C(beta) atom of Ala172 and the thermostablity of the enzyme shows a good correlation with the hydrophobicity of the substituted residues. Substitution of Ala172 by the 'longer' residues Leu or Phe causes a rearrangement of the domain structure, which leads to a higher thermostability of the enzymes than that expected from the hydrophobicity of the substituted residues. Mutation of Ala172 to negatively charged residues gave an unexpected result: the melting temperature of the Asp mutant enzyme was reduced by 2.7 K while that of the Glu mutant increased by 1.8 K. Molecular-modelling studies indicated that the glutamate side chain was sufficiently long that it did not act as a buried charge as did the aspartate, but instead protruded to the outside of the hydrophobic cavity and contributed to the stability of the enzyme by enhancing the packing of the local side chains and forming an extra salt bridge with the side chain of Lys175.
Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus.,Qu C, Akanuma S, Tanaka N, Moriyama H, Oshima T Acta Crystallogr D Biol Crystallogr. 2001 Feb;57(Pt 2):225-32. PMID:11173468[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Qu C, Akanuma S, Tanaka N, Moriyama H, Oshima T. Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus. Acta Crystallogr D Biol Crystallogr. 2001 Feb;57(Pt 2):225-32. PMID:11173468
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