View source for 6xki


==Crystal structure of eIF4A-I in complex with RNA bound to des-MePateA, a pateamine A analog==
<StructureSection load='6xki' size='340' side='right'caption='[[6xki]], [[Resolution|resolution]] 2.87&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xki]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XKI 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]] 2.87&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=V6D:(3S,6Z,8E,11S,15R)-15-amino-3-[(1E,3E,5E)-7-(dimethylamino)-2,5-dimethylhepta-1,3,5-trien-1-yl]-9,11-dimethyl-4,12-dioxa-20-thia-21-azabicyclo[16.2.1]henicosa-1(21),6,8,18-tetraene-5,13-dione'>V6D</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=6xki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xki OCA], [https://pdbe.org/6xki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xki RCSB], [https://www.ebi.ac.uk/pdbsum/6xki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xki ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IF4A1_MOUSE IF4A1_MOUSE] ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interfacial inhibitors exert their biological effects through co-association with two macromolecules. The pateamine A (PatA) class of molecules function by stabilizing eukaryotic initiation factor (eIF) 4A RNA helicase onto RNA, resulting in translation initiation inhibition. Here, we present the crystal structure of an eIF4A1:RNA complex bound to an analog of the marine sponge-derived natural product PatA, C5-desmethyl PatA (DMPatA). One end of this small molecule wedges itself between two RNA bases while the other end is cradled by several protein residues. Strikingly, DMPatA interacts with the eIF4A1:RNA complex in an almost identical fashion as rocaglamide A (RocA), despite being completely unrelated from a structural standpoint. The structural data rationalize the ability of PatA analogs to target a wider range of RNA substrates compared to RocA. We define the molecular basis of how DMPatA is able to clamp eIF4A1 onto RNA, imparting potent inhibitory properties to this molecule.

Functional mimicry revealed by the crystal structure of an eIF4A:RNA complex bound to the interfacial inhibitor, desmethyl pateamine A.,Naineni SK, Liang J, Hull K, Cencic R, Zhu M, Northcote P, Teesdale-Spittle P, Romo D, Nagar B, Pelletier J Cell Chem Biol. 2021 Jun 17;28(6):825-834.e6. doi: , 10.1016/j.chembiol.2020.12.006. Epub 2021 Jan 6. PMID:33412110<ref>PMID:33412110</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xki" style="background-color:#fffaf0;"></div>

==See Also==
*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Liang J]]
[[Category: Nagar B]]
[[Category: Naineni SK]]
[[Category: Pelletier J]]