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==H.influenzae TrmD in complex with N-(4-{[(1H-IMIDAZOL-2-YLMETHYL)AMINO]METHYL}BENZYL)-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-5-CARBOXAMIDE==
==H.influenzae TrmD in complex with N-(4-{[(1H-IMIDAZOL-2-YLMETHYL)AMINO]METHYL}BENZYL)-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-5-CARBOXAMIDE==
<StructureSection load='4mcb' size='340' side='right' caption='[[4mcb]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
<StructureSection load='4mcb' size='340' side='right'caption='[[4mcb]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4mcb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Haemophilus_influenzae_rd_kw20 Haemophilus influenzae rd kw20]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MCB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MCB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4mcb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Haemophilus_influenzae_Rd_KW20 Haemophilus influenzae Rd KW20]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MCB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MCB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=21W:N-(4-{[(1H-IMIDAZOL-2-YLMETHYL)AMINO]METHYL}BENZYL)-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-5-CARBOXAMIDE'>21W</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.94&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4mcc|4mcc]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21W:N-(4-{[(1H-IMIDAZOL-2-YLMETHYL)AMINO]METHYL}BENZYL)-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDINE-5-CARBOXAMIDE'>21W</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HI_0202, trmD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=71421 Haemophilus influenzae Rd KW20])</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=4mcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mcb OCA], [https://pdbe.org/4mcb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mcb RCSB], [https://www.ebi.ac.uk/pdbsum/4mcb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mcb ProSAT]</span></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(37)-N(1))-methyltransferase tRNA (guanine(37)-N(1))-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.228 2.1.1.228] </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=4mcb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mcb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mcb RCSB], [http://www.ebi.ac.uk/pdbsum/4mcb PDBsum]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/TRMD_HAEIN TRMD_HAEIN] Specifically methylates guanosine-37 in various tRNAs (By similarity).[HAMAP-Rule:MF_00605]
The t-RNA-(N1G37) methyl transferase (TrmD) is essential for growth and highly conserved in both Gram-positive and Gram-negative bacterial pathogens. Additionally, TrmD is very distinct from its human ortholog TRM5, and thus is a suitable target for the design of novel antibacterials. Screening of a collection of compound fragments using Haemophilus influenzae TrmD identified inhibitory, fused thieno-pyrimidones that were competitive with S-adenosylmethionine (SAM), the physiological methyl donor substrate. Guided by x-ray co-crystal structures, fragment 1 was elaborated into a nanomolar inhibitor of a broad range of Gram-negative TrmD isozymes. These compounds demonstrated no activity against representative human SAM utilizing enzymes, PRMT1 and SET7/9. This is the first report of selective, nanomolar inhibitors of TrmD with demonstrated ability to order the TrmD lid in the absence of tRNA.
 
Selective Inhibitors of Bacterial t-RNA-(NG37) Methyltransferase (TrmD) that Demonstrate Novel Ordering of the Lid Domain.,Hill PJ, Abibi A, Albert R, Andrews B, Gagnon MM, Gao N, Grebe T, Hajec LI, Huang J, Livchak S, Lahiri SD, McKinney DC, Thresher J, Wang H, Olivier N, Buurman ET J Med Chem. 2013 Aug 27. PMID:23981144<ref>PMID:23981144</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[TRNA methyltransferase|TRNA methyltransferase]]
*[[TRNA methyltransferase 3D structures|TRNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Haemophilus influenzae rd kw20]]
[[Category: Haemophilus influenzae Rd KW20]]
[[Category: Hill, P]]
[[Category: Large Structures]]
[[Category: Olivier, N B]]
[[Category: Hill P]]
[[Category: Hmt]]
[[Category: Olivier NB]]
[[Category: Methyl transferase to trna]]
[[Category: Sah]]
[[Category: Sam]]
[[Category: Sinefungin]]
[[Category: Structural genomic]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Trefoil]]
[[Category: Trefoil knot]]
[[Category: Trmd]]
[[Category: Trna]]

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