View source for 7ndz


==ThyX reconstituted with N5-carbinolamine flavin==
<StructureSection load='7ndz' size='340' side='right'caption='[[7ndz]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ndz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NDZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NDZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FDA:DIHYDROFLAVINE-ADENINE+DINUCLEOTIDE'>FDA</scene>, <scene name='pdbligand=HUF:[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2R,3S,4S)-5-[5-methanoyl-7,8-dimethyl-2,4-bis(oxidanylidene)-1H-benzo[g]pteridin-10-yl]-2,3,4-tris(oxidanyl)pentyl]+hydrogen+phosphate'>HUF</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=7ndz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ndz OCA], [https://pdbe.org/7ndz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ndz RCSB], [https://www.ebi.ac.uk/pdbsum/7ndz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ndz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/THYX_THEMA THYX_THEMA] Catalyzes the formation of dTMP and tetrahydrofolate from dUMP and methylenetetrahydrofolate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Folate enzyme cofactors and their derivatives have the unique ability to provide a single carbon unit at different oxidation levels for the de novo synthesis of amino-acids, purines, or thymidylate, an essential DNA nucleotide. How these cofactors mediate methylene transfer is not fully settled yet, particularly with regard to how the methylene is transferred to the methylene acceptor. Here, we uncovered that the bacterial thymidylate synthase ThyX, which relies on both folate and flavin for activity, can also use a formaldehyde-shunt to directly synthesize thymidylate. Combining biochemical, spectroscopic and anaerobic crystallographic analyses, we showed that formaldehyde reacts with the reduced flavin coenzyme to form a carbinolamine intermediate used by ThyX for dUMP methylation. The crystallographic structure of this intermediate reveals how ThyX activates formaldehyde and uses it, with the assistance of active site residues, to methylate dUMP. Our results reveal that carbinolamine species promote methylene transfer and suggest that the use of a CH2O-shunt may be relevant in several other important folate-dependent reactions.

An enzymatic activation of formaldehyde for nucleotide methylation.,Bou-Nader C, Stull FW, Pecqueur L, Simon P, Guerineau V, Royant A, Fontecave M, Lombard M, Palfey BA, Hamdane D Nat Commun. 2021 Jul 27;12(1):4542. doi: 10.1038/s41467-021-24756-8. PMID:34315871<ref>PMID:34315871</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ndz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Thymidylate synthase 3D structures|Thymidylate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermotoga maritima]]
[[Category: Bou-Nader C]]
[[Category: Hamdane D]]
[[Category: Pecqueur L]]