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==Binding and structural studies of a 5,5-difluoromethyl adenosine nucleoside with the fluorinase enzyme==
<StructureSection load='5fiu' size='340' side='right'caption='[[5fiu]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fiu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_cattleya Streptomyces cattleya]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FIU 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]] 1.84&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=Y3J:5,5-DIFLUOROMETHYL+ADENOSINE'>Y3J</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=5fiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fiu OCA], [https://pdbe.org/5fiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fiu RCSB], [https://www.ebi.ac.uk/pdbsum/5fiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fiu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FLA_STRCT FLA_STRCT] Involved in the biosynthesis of fluorometabolites. Catalyzes the formation of a C-F bond by combining S-adenosyl-L-methionine (SAM) and fluoride to generate 5'-fluoro-5'-deoxyadenosine (5'-FDA) and L-methionine. It can also use 2'-deoxyadenosine in place of adenosine as substrate.<ref>PMID:12860396</ref> <ref>PMID:14765200</ref> <ref>PMID:16370017</ref> <ref>PMID:16604208</ref> <ref>PMID:16720268</ref> <ref>PMID:17985882</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The investigation of a difluoromethyl-bearing nucleoside with the fluorinase enzyme is described. 5',5'-Difluoro-5'-deoxyadenosine 7 (F2DA) was synthesised from adenosine, and found to bind to the fluorinase enzyme by isothermal titration calorimetry with similar affinity compared to 5'-fluoro-5'-deoxyadenosine 2 (FDA), the natural product of the enzymatic reaction. F2DA7 was found, however, not to undergo the enzyme catalysed reaction with l-selenomethionine, unlike FDA 2, which undergoes reaction with l-selenomethionine to generate Se-adenosylselenomethionine. A co-crystal structure of the fluorinase and F2DA7 and tartrate was solved to 1.8A, and revealed that the difluoromethyl group bridges interactions known to be essential for activation of the single fluorine in FDA 2. An unusual hydrogen bonding interaction between the hydrogen of the difluoromethyl group and one of the hydroxyl oxygens of the tartrate ligand was also observed. The bridging interactions, coupled with the inherently stronger C-F bond in the difluoromethyl group, offers an explanation for why no reaction is observed.

Exploration of a potential difluoromethyl-nucleoside substrate with the fluorinase enzyme.,Thompson S, McMahon SA, Naismith JH, O'Hagan D Bioorg Chem. 2015 Nov 18;64:37-41. doi: 10.1016/j.bioorg.2015.11.003. PMID:26642178<ref>PMID:26642178</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5fiu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces cattleya]]
[[Category: McMahon SA]]
[[Category: Naismith JH]]
[[Category: O'Hagan D]]
[[Category: Thompson S]]