View source for 6bxl


==Crystal structure of Pyrococcus horikoshii Dph2 with 4Fe-4S cluster and SAM==
<StructureSection load='6bxl' size='340' side='right'caption='[[6bxl]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6bxl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_horikoshii_OT3 Pyrococcus horikoshii OT3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BXL 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]] 2.301&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</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=6bxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bxl OCA], [https://pdbe.org/6bxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bxl RCSB], [https://www.ebi.ac.uk/pdbsum/6bxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bxl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPH2_PYRHO DPH2_PYRHO] Catalyzes the first step of diphthamide biosynthesis, i.e. the transfer of the 3-amino-3-carboxypropyl group from S-adenosyl-L-methionine (SAM) to the C2 position of the imidazole ring of the target histidine residue in translation elongation factor 2 (EF-2).<ref>PMID:20559380</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.

Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.,Dong M, Kathiresan V, Fenwick MK, Torelli AT, Zhang Y, Caranto JD, Dzikovski B, Sharma A, Lancaster KM, Freed JH, Ealick SE, Hoffman BM, Lin H Science. 2018 Mar 16;359(6381):1247-1250. doi: 10.1126/science.aao6595. PMID:29590073<ref>PMID:29590073</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6bxl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pyrococcus horikoshii OT3]]
[[Category: Carantoa JD]]
[[Category: Dong M]]
[[Category: Dzikovski B]]
[[Category: Ealick SE]]
[[Category: Fenwick MK]]
[[Category: Freed JH]]
[[Category: Hoffman BM]]
[[Category: Kathiresan V]]
[[Category: Lancaster KM]]
[[Category: Lin H]]
[[Category: Torelli AT]]
[[Category: Zhang Y]]