5dk4
From Proteopedia
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| - | ''' | + | ==Crystal structure analysis of Tryptophanyl-trna synthetase from Bacillus stearothermophilus in complex with indolmycin and Mg*ATP== |
| + | <StructureSection load='5dk4' size='340' side='right' caption='[[5dk4]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5dk4]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DK4 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5BX:(5S)-5-[(1R)-1-(1H-INDOL-3-YL)ETHYL]-2-(METHYLAMINO)-1,3-OXAZOL-4(5H)-ONE'>5BX</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Tryptophan--tRNA_ligase Tryptophan--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.2 6.1.1.2] </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=5dk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dk4 OCA], [http://pdbe.org/5dk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dk4 RCSB], [http://www.ebi.ac.uk/pdbsum/5dk4 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Indolmycin is a natural tryptophan analog that competes with tryptophan for binding to tryptophanyl-tRNA synthetase (TrpRS) enzymes. Bacterial and eukaryotic cytosolic TrpRSs have comparable affinities for tryptophan, Km ~2 muM, and yet only bacterial TrpRSs are inhibited by indolmycin. Despite the similarity between these ligands, Bacillus stearothermophilus (Bs)TrpRS preferentially binds indolmycin ~1500-fold tighter than its tryptophan substrate. Kinetic characterization and crystallographic analysis of BsTrpRS allowed us to probe novel aspects of indolmycin inhibitory action. Previous work had revealed that long-range coupling to residues within an allosteric region called the D1 switch of BsTrpRS positions the Mg2+ ion in a manner that allows it to assist in transition-state stabilization. The Mg2+ ion in the inhibited complex forms significantly closer contacts with non-bridging oxygen atoms from each phosphate group of ATP and three water molecules than occur in the (presumably catalytically competent) pre-transition state (preTS) crystal structures. We propose that this altered coordination, stabilizes a ground-state Mg2+.ATP configuration, accounting for the high-affinity inhibition of BsTrpRS by indolmycin. Conversely, both the ATP configuration and Mg2+ coordination in the human cytosolic (Hc)TrpRS preTS structure differ greatly from the BsTrpRS preTS structure. The effect of these differences is that catalysis occurs via a different transition state stabilization mechanism in HcTrpRS, with a yet-to-be determined role for Mg2+. Modeling indolmycin into the tryptophan binding site points to steric hindrance and an inability to retain the interactions used for tryptophan substrate recognition as causes for the 1000-fold weaker indolmycin affinity to HcTrpRS. | ||
| - | + | Selective Inhibition of Bacterial Tryptophanyl-tRNA Synthetases by Indolmycin is Mechanism-Based.,Williams TL, Yin WY, Carter CW Jr J Biol Chem. 2015 Nov 9. pii: jbc.M115.690321. PMID:26555258<ref>PMID:26555258</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5dk4" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: Carter | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Tryptophan--tRNA ligase]] | ||
| + | [[Category: Carter, C W]] | ||
[[Category: Williams, T]] | [[Category: Williams, T]] | ||
| - | [[Category: Yin, W | + | [[Category: Yin, W Y]] |
| - | [[Category: | + | [[Category: Aar]] |
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
Revision as of 19:26, 30 November 2015
Crystal structure analysis of Tryptophanyl-trna synthetase from Bacillus stearothermophilus in complex with indolmycin and Mg*ATP
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