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5zk5

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'''Unreleased structure'''
 
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The entry 5zk5 is ON HOLD until Paper Publication
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==Stapled-peptides tailored against initiation of translation==
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<StructureSection load='5zk5' size='340' side='right'caption='[[5zk5]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5zk5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZK5 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zk5 OCA], [https://pdbe.org/5zk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zk5 RCSB], [https://www.ebi.ac.uk/pdbsum/5zk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zk5 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IF4G1_HUMAN IF4G1_HUMAN] Defects in EIF4G1 are the cause of Parkinson disease type 18 (PARK18) [MIM:[https://omim.org/entry/614251 614251]. An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:21907011</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/IF4G1_HUMAN IF4G1_HUMAN] Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Stapled-peptides have emerged as an exciting class of molecules which can modulate protein-protein interactions. We have used a structure-guided approach to rationally develop a set of hydrocarbon stapled-peptides with high binding affinities and residence times against the oncogenic eukaryotic translation initiation factor 4E (eIF4E) protein. Crystal structures of these peptides in complex with eIF4E show that they form specific interactions with a region on the protein-binding interface of eIF4E which is distinct from the other well-established canonical interactions. This recognition element is a major molecular determinant underlying the improved binding kinetics of these peptides with eIF4E. The interactions were further exploited by designing features in the peptides to attenuate disorder and increase helicity which collectively resulted in the generation of a distinct class of hydrocarbon stapled-peptides targeting eIF4E. This study details new insights into the molecular basis of stapled-peptide: eIF4E interactions and their exploitation to enhance promising lead molecules for the development of stapled-peptide compounds for oncology.
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Authors: Lama, D., Liberator, A., Frosi, Y., Nakhle, J., Tsomia, N., Bashir, T., Lane, D.P., Brown, C.J., Verma, C.S., Auvin, S., Ciesielski, F., Uhring, M.
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Structural insights reveal a recognition feature for tailoring hydrocarbon stapled-peptides against the eukaryotic translation initiation factor 4E protein.,Lama D, Liberatore AM, Frosi Y, Nakhle J, Tsomaia N, Bashir T, Lane DP, Brown CJ, Verma CS, Auvin S Chem Sci. 2019 Jan 7;10(8):2489-2500. doi: 10.1039/c8sc03759k. eCollection 2019, Feb 28. PMID:30881679<ref>PMID:30881679</ref>
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Description: Stapled-peptides tailored against initiation of translation
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Ciesielski, F]]
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<div class="pdbe-citations 5zk5" style="background-color:#fffaf0;"></div>
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[[Category: Brown, C.J]]
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[[Category: Tsomia, N]]
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==See Also==
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[[Category: Nakhle, J]]
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*[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]]
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[[Category: Frosi, Y]]
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== References ==
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[[Category: Verma, C.S]]
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<references/>
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[[Category: Lama, D]]
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__TOC__
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[[Category: Liberator, A]]
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</StructureSection>
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[[Category: Auvin, S]]
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[[Category: Homo sapiens]]
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[[Category: Uhring, M]]
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[[Category: Large Structures]]
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[[Category: Bashir, T]]
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[[Category: Auvin S]]
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[[Category: Lane, D.P]]
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[[Category: Bashir T]]
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[[Category: Brown CJ]]
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[[Category: Ciesielski F]]
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[[Category: Frosi Y]]
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[[Category: Lama D]]
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[[Category: Lane DP]]
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[[Category: Liberator A]]
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[[Category: Nakhle J]]
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[[Category: Tsomia N]]
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[[Category: Uhring M]]
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[[Category: Verma CS]]

Current revision

Stapled-peptides tailored against initiation of translation

PDB ID 5zk5

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