5dk4: Difference between revisions

← Older edit Newer edit →

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==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]] 1.90&Aring;' 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.
-The entry 5dk4 is ON HOLD  until Paper Publication
+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>
-Authors: Williams, T., Yin, W.Y., Carter Jr., C.W.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+<div class="pdbe-citations 5dk4" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Carter Jr]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Tryptophan--tRNA ligase]]
+[[Category: Carter, C W]]
 [[Category: Williams, T]]
-[[Category: Yin, W.Y]]
+[[Category: Yin, W Y]]
-[[Category: C.W]]
+[[Category: Aar]]
+[[Category: Inhibitor]]
+[[Category: Ligase-ligase inhibitor complex]]