4fzb: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4fzb]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Paramecium_bursaria_Chlorella_virus_1 Paramecium bursaria Chlorella virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FZB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4fzb]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Paramecium_bursaria_Chlorella_virus_1 Paramecium bursaria Chlorella virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FZB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0VJ:2-HYDROXY-3-(4-METHOXYBENZYL)NAPHTHALENE-1,4-DIONE'>0VJ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 2.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0VJ:2-HYDROXY-3-(4-METHOXYBENZYL)NAPHTHALENE-1,4-DIONE'>0VJ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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=4fzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fzb OCA], [https://pdbe.org/4fzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fzb RCSB], [https://www.ebi.ac.uk/pdbsum/4fzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fzb 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=4fzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fzb OCA], [https://pdbe.org/4fzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fzb RCSB], [https://www.ebi.ac.uk/pdbsum/4fzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fzb ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/THYX_PBCV1 THYX_PBCV1] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate (By similarity).
[https://www.uniprot.org/uniprot/THYX_PBCV1 THYX_PBCV1] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nature has established two mechanistically and structurally unrelated families of thymidylate synthases that produce de novo thymidylate or dTMP, an essential DNA precursor. Representatives of the alternative flavin-dependent thymidylate synthase family, ThyX, are found in a large number of microbial genomes, but are absent in humans. We have exploited the nucleotide binding pocket of ThyX proteins to identify non-substrate-based tight-binding ThyX inhibitors that inhibited growth of genetically modified Escherichia coli cells dependent on thyX in a manner mimicking a genetic knockout of thymidylate synthase. We also solved the crystal structure of a viral ThyX bound to 2-hydroxy-3-(4-methoxybenzyl)-1,4-naphthoquinone at a resolution of 2.6 A. This inhibitor was found to bind within the conserved active site of the tetrameric ThyX enzyme, at the interface of two monomers, partially overlapping with the dUMP binding pocket. Our studies provide new chemical tools for investigating the ThyX reaction mechanism and establish a novel mechanistic and structural basis for inhibition of thymidylate synthesis. As essential ThyX proteins are found e.g. in Mycobacterium tuberculosis and Helicobacter pylori, our studies have also potential to pave the way towards the development of new anti-microbial compounds.
Mechanistic and structural basis for inhibition of thymidylate synthase ThyX.,Basta T, Boum Y, Briffotaux J, Becker HF, Lamarre-Jouenne I, Lambry JC, Skouloubris S, Liebl U, Graille M, van Tilbeurgh H, Myllykallio H Open Biol. 2012 Oct;2(10):120120. doi: 10.1098/rsob.120120. PMID:23155486<ref>PMID:23155486</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4fzb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
</StructureSection>
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