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| | <StructureSection load='7a6d' size='340' side='right'caption='[[7a6d]], [[Resolution|resolution]] 1.59Å' scene=''> | | <StructureSection load='7a6d' size='340' side='right'caption='[[7a6d]], [[Resolution|resolution]] 1.59Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7a6d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Zymmo Zymmo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A6D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7a6d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Zymomonas_mobilis_subsp._mobilis_ZM4_=_ATCC_31821 Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7A6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7A6D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R1E:trans-4,4-difluorocyclopentane-1,2-diol'>R1E</scene>, <scene name='pdbligand=RGN:(1~{R},2~{R})-4,4-bis(fluoranyl)cyclopentane-1,2-diol'>RGN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.59Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7a0b|7a0b]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=R1E:trans-4,4-difluorocyclopentane-1,2-diol'>R1E</scene>, <scene name='pdbligand=RGN:(1~{R},2~{R})-4,4-bis(fluoranyl)cyclopentane-1,2-diol'>RGN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tgt, ZMO0363 ([https://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'>[https://en.wikipedia.org/wiki/tRNA-guanine(34)_transglycosylase tRNA-guanine(34) transglycosylase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=7a6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a6d OCA], [https://pdbe.org/7a6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a6d RCSB], [https://www.ebi.ac.uk/pdbsum/7a6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a6d ProSAT]</span></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=7a6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7a6d OCA], [https://pdbe.org/7a6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7a6d RCSB], [https://www.ebi.ac.uk/pdbsum/7a6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7a6d ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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]
| + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 7a6d" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7a6d" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[TRNA-guanine transglycosylase 3D structures|TRNA-guanine transglycosylase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Zymmo]] | + | [[Category: Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821]] |
| - | [[Category: Heine, A]] | + | [[Category: Heine A]] |
| - | [[Category: Klebe, G]] | + | [[Category: Klebe G]] |
| - | [[Category: Nguyen, D]] | + | [[Category: Nguyen D]] |
| - | [[Category: Disulfide]]
| + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Fragment]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
7a6d is a 1 chain structure with sequence from Zymomonas mobilis subsp. mobilis ZM4 = ATCC 31821. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.59Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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]
Publication Abstract from PubMed
Interference with protein-protein interfaces represents an attractive as well as challenging option for therapeutic intervention and drug design. The enzyme tRNA-guanine transglycosylase, a target to fight Shigellosis, is only functional as a homodimer. Although we previously produced monomeric variants by site-directed mutagenesis, we only crystallized the functional dimer, simply because upon crystallization the local protein concentration increases and favors formation of the dimer interface, which represents an optimal and highly stable packing of the protein in the solid state. Unfortunately, this prevents access to structural information about the interface geometry in its monomeric state and complicates the development of modulators that can interfere with and prevent dimer formation. Here, we report on a cysteine-containing protein variant in which, under oxidizing conditions, a disulfide linkage is formed. This reinforces a novel packing geometry of the enzyme. In this captured quasi-monomeric state, the monomer units arrange in a completely different way and, thus, expose a loop-helix motif, originally embedded into the old interface, now to the surface. The motif adopts a geometry incompatible with the original dimer formation. Via the soaking of fragments into the crystals, we identified several hits accommodating a cryptic binding site next to the loop-helix motif and modulated its structural features. Our study demonstrates the druggability of the interface by breaking up the homodimeric protein using an introduced disulfide cross-link. By rational concepts, we increased the potency of these fragments to a level where we confirmed their binding by NMR to a nondisulfide-linked TGT variant. The idea of intermediately introducing a disulfide linkage may serve as a general concept of how to transform a homodimer interface into a quasi-monomeric state and give access to essential structural and design information.
Targeting a Cryptic Pocket in a Protein-Protein Contact by Disulfide-Induced Rupture of a Homodimeric Interface.,Nguyen D, Xie X, Jakobi S, Terwesten F, Metz A, Nguyen TXP, Palchykov VA, Heine A, Reuter K, Klebe G ACS Chem Biol. 2021 Jun 3. doi: 10.1021/acschembio.1c00296. PMID:34081441[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nguyen D, Xie X, Jakobi S, Terwesten F, Metz A, Nguyen TXP, Palchykov VA, Heine A, Reuter K, Klebe G. Targeting a Cryptic Pocket in a Protein-Protein Contact by Disulfide-Induced Rupture of a Homodimeric Interface. ACS Chem Biol. 2021 Jun 3. doi: 10.1021/acschembio.1c00296. PMID:34081441 doi:http://dx.doi.org/10.1021/acschembio.1c00296
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