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| | <StructureSection load='4q4r' size='340' side='right'caption='[[4q4r]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='4q4r' size='340' side='right'caption='[[4q4r]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4q4r]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Zymmo Zymmo]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3v0y 3v0y] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3gfn 3gfn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q4R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Q4R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4q4r]] 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]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3v0y 3v0y] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3gfn 3gfn]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Q4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Q4R FirstGlance]. <br> |
| - | </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=SQO:2-{[2-(4-MORPHOLINYL)ETHYL]AMINO}-1,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>SQO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SQO:2-{[2-(4-MORPHOLINYL)ETHYL]AMINO}-1,7-DIHYDRO-8H-IMIDAZO[4,5-G]QUINAZOLIN-8-ONE'>SQO</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">[[4q4m|4q4m]], [[4q4o|4q4o]], [[4q4p|4q4p]], [[4q4q|4q4q]], [[4q4s|4q4s]], [[1p0d|1p0d]]</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=4q4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q4r OCA], [https://pdbe.org/4q4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4q4r RCSB], [https://www.ebi.ac.uk/pdbsum/4q4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4q4r ProSAT]</span></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4q4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q4r OCA], [http://pdbe.org/4q4r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q4r RCSB], [http://www.ebi.ac.uk/pdbsum/4q4r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q4r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == 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] | + | [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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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[TRNA-guanine transglycosylase|TRNA-guanine transglycosylase]] | + | *[[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: Neeb, M]] | + | [[Category: Neeb M]] |
| - | [[Category: Guanine exchange enzyme]]
| + | |
| - | [[Category: Preq1]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| - | [[Category: Trna]]
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| Structural highlights
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
Lead optimization focuses on binding-affinity improvement. If a flat structure-activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.
Beyond Affinity: Enthalpy-Entropy Factorization Unravels Complexity of a Flat Structure-Activity Relationship for Inhibition of a tRNA-Modifying Enzyme.,Neeb M, Betz M, Heine A, Barandun LJ, Hohn C, Diederich F, Klebe G J Med Chem. 2014 Jun 24. PMID:24960372[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Neeb M, Betz M, Heine A, Barandun LJ, Hohn C, Diederich F, Klebe G. Beyond Affinity: Enthalpy-Entropy Factorization Unravels Complexity of a Flat Structure-Activity Relationship for Inhibition of a tRNA-Modifying Enzyme. J Med Chem. 2014 Jun 24. PMID:24960372 doi:http://dx.doi.org/10.1021/jm5006868
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