View source for 4htb


==tRNA-guanine transglycosylase Y330C mutant in space group C2==
<StructureSection load='4htb' size='340' side='right'caption='[[4htb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4htb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Zymmo Zymmo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HTB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4HTB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3unt|3unt]], [[4dxx|4dxx]], [[4dy1|4dy1]], [[3uvi|3uvi]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tgt, ZMO0363 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=264203 ZYMMO])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/tRNA-guanine(34)_transglycosylase tRNA-guanine(34) transglycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.29 2.4.2.29] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=4htb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htb OCA], [http://pdbe.org/4htb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4htb RCSB], [http://www.ebi.ac.uk/pdbsum/4htb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4htb ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/TGT_ZYMMO TGT_ZYMMO]] Exchanges the guanine residue with 7-aminomethyl-7-deazaguanine in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr). After this exchange, a cyclopentendiol moiety is attached to the 7-aminomethyl group of 7-deazaguanine, resulting in the hypermodified nucleoside queuosine (Q) (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).[HAMAP-Rule:MF_00168] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Shigella bacteria constitute the causative agent of bacillary dysentery, an acute inflammatory disease causing the death of more than one million humans per year. A null mutation in the tgt gene encoding the tRNA-modifying enzyme tRNA-guanine transglycosylase (Tgt) was found to drastically decrease the pathogenicity of Shigella bacteria, suggesting the use of Tgt as putative target for selective antibiotics. The enzyme is only functionally active as a homodimer; thus, interference with the formation of its protein-protein interface is an attractive opportunity for therapeutic intervention. To better understand the driving forces responsible for the assembly, stability, and formation of the homodimer, we studied the properties of the residues that establish the dimer interface in detail. We performed site-directed mutagenesis and controlled shifts in the monomer/dimer equilibrium ratio in solution in a concentration-dependent manner by native mass spectrometry and used crystal structure analysis to elucidate the geometrical modulations resulting from mutational variations. The wild-type enzyme exhibits nearly exclusive dimer geometry. A patch of four aromatic amino acids, embedded into a ring of hydrophobic residues and further stabilized by a network of H-bonds, is essential for the stability of the dimer's contact. Accordingly, any perturbance in the constitution of this aromatic patch by nonaromatic residues reduces dimer stability significantly, with some of these exchanges resulting in a nearly exclusively monomeric state. Apart from the aromatic hot spot, the interface comprises an extended loop-helix motif that exhibits remarkable flexibility. In the destabilized mutated variants, the loop-helix motif adopts deviating conformations in the interface region, and a number of water molecules, penetrating into the interface, are observed.

What Glues a Homodimer Together: Systematic Analysis of the Stabilizing Effect of an Aromatic Hot Spot in the Protein-Protein Interface of the tRNA-Modifying Enzyme Tgt.,Jakobi S, Nguyen PT, Debaene F, Cianferani S, Reuter K, Klebe G ACS Chem Biol. 2015 Aug 21;10(8):1897-907. doi: 10.1021/acschembio.5b00028. Epub , 2015 May 26. PMID:25951081<ref>PMID:25951081</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4htb" style="background-color:#fffaf0;"></div>

==See Also==
*[[TRNA-guanine transglycosylase|TRNA-guanine transglycosylase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Zymmo]]
[[Category: Jakobi, S]]
[[Category: Klebe, G]]
[[Category: Dimer interface]]
[[Category: Guanine]]
[[Category: Protein-protein-interface]]
[[Category: Tgt]]
[[Category: Transferase]]
[[Category: Trna]]