3rmj
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of truncated alpha-Isopropylmalate Synthase from Neisseria meningitidis== | |
| - | + | <StructureSection load='3rmj' size='340' side='right' caption='[[3rmj]], [[Resolution|resolution]] 1.95Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3rmj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Neimi Neimi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RMJ FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sr9|1sr9]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">leuA, NMB1070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=491 NEIMI])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-isopropylmalate_synthase 2-isopropylmalate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.13 2.3.3.13] </span></td></tr> | ||
| + | <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=3rmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rmj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rmj RCSB], [http://www.ebi.ac.uk/pdbsum/3rmj PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://www.uniprot.org/uniprot/LEU1_NEIMB LEU1_NEIMB]] Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate) (By similarity). | [[http://www.uniprot.org/uniprot/LEU1_NEIMB LEU1_NEIMB]] Catalyzes the condensation of the acetyl group of acetyl-CoA with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-hydroxy-4-methylpentanoate (2-isopropylmalate) (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | alpha-Isopropylmalate synthase (alpha-IPMS) catalyzes the metal-dependent aldol reaction between alpha-ketoisovalerate (alpha-KIV) and acetyl-coenzyme A (AcCoA) to give alpha-isopropylmalate (alpha-IPM). This reaction is the first committed step in the biosynthesis of leucine in bacteria. alpha-IPMS is homodimeric, with monomers consisting of (beta/alpha)(8) barrel catalytic domains fused to a C-terminal regulatory domain, responsible for binding leucine and providing feedback regulation for leucine biosynthesis. In these studies, we demonstrate that removal of the regulatory domain from the alpha-IPMS enzymes of both Neisseria meningitidis (NmeIPMS) and Mycobacterium tuberculosis (MtuIPMS) results in enzymes that are unable to catalyze the formation of alpha-IPM, although truncated NmeIPMS was still able to slowly hydrolyze AcCoA. The lack of catalytic activity of these truncation variants was confirmed by complementation studies with Escherichia coli cells lacking the alpha-IPMS gene, where transformation with the plasmids encoding the truncated alpha-IPMS enzymes was not able to rescue alpha-IPMS activity. X-ray crystal structures of both truncation variants reveal that both proteins are dimeric and that the catalytic sites of the proteins are intact, although the divalent metal ion that is thought to be responsible for activating substrate alpha-KIV is displaced slightly relative to its position in the substrate-bound, wild-type structure. Isothermal titration calorimetry and WaterLOGSY nuclear magnetic resonance experiments demonstrate that although these truncation variants are not able to catalyze the reaction between alpha-KIV and AcCoA, they are still able to bind the substrate alpha-KIV. It is proposed that the regulatory domain is crucial for ensuring protein dynamics necessary for competent catalysis. | ||
| - | + | Removal of the C-Terminal Regulatory Domain of alpha-Isopropylmalate Synthase Disrupts Functional Substrate Binding.,Huisman FH, Koon N, Bulloch EM, Baker HM, Baker EN, Squire CJ, Parker EJ Biochemistry. 2012 Mar 6. PMID:22352945<ref>PMID:22352945</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: 2-isopropylmalate synthase]] | [[Category: 2-isopropylmalate synthase]] | ||
[[Category: Neimi]] | [[Category: Neimi]] | ||
| - | [[Category: Baker, E N | + | [[Category: Baker, E N]] |
| - | [[Category: Baker, H M | + | [[Category: Baker, H M]] |
| - | [[Category: Huisman, F H.A | + | [[Category: Huisman, F H.A]] |
| - | [[Category: Koon, N | + | [[Category: Koon, N]] |
| - | [[Category: Parker, E J | + | [[Category: Parker, E J]] |
[[Category: Acetyl coenzyme some]] | [[Category: Acetyl coenzyme some]] | ||
[[Category: Alpha-ketoisovalerate]] | [[Category: Alpha-ketoisovalerate]] | ||
Revision as of 11:19, 25 December 2014
Crystal structure of truncated alpha-Isopropylmalate Synthase from Neisseria meningitidis
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