6p4v

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'''Unreleased structure'''
 
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The entry 6p4v is ON HOLD until Paper Publication
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==1.65 Angstrom ternary complex of Deoxyhypusine synthase with cofactor NAD and spermidine mimic inhibitor GC7==
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<StructureSection load='6p4v' size='340' side='right'caption='[[6p4v]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6p4v]] 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=6P4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P4V 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]] 1.65&#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=GC7:1-GUANIDINIUM-7-AMINOHEPTANE'>GC7</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=6p4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p4v OCA], [https://pdbe.org/6p4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p4v RCSB], [https://www.ebi.ac.uk/pdbsum/6p4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p4v ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DHYS_HUMAN DHYS_HUMAN] Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Deoxyhypusine synthase (DHPS) utilizes spermidine and NAD as cofactors to incorporate a hypusine modification into the eukaryotic translation initiation factor 5A (eIF5A). Hypusine is essential for eIF5A activation, which, in turn, plays a key role in regulating protein translation of selected mRNA that are associated with the synthesis of oncoproteins, thereby enhancing tumor cell proliferation. Therefore, inhibition of DHPS is a promising therapeutic option for the treatment of cancer. To discover novel lead compounds that target DHPS, we conducted synthetic studies with a hit obtained via high-throughput screening. Optimization of the ring structures of the amide compound (2) led to bromobenzothiophene (11g) with potent inhibitory activity against DHPS. X-ray crystallographic analysis of 11g complexed with DHPS revealed a dramatic conformational change in DHPS, which suggests the presence of a novel allosteric site. These findings provide the basis for the development of novel therapy distinct from spermidine mimetic inhibitors.
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Authors: Klein, M.G., Ambrus-Aikelin, G.
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Discovery of Novel Allosteric Inhibitors of Deoxyhypusine Synthase.,Tanaka Y, Kurasawa O, Yokota A, Klein MG, Ono K, Saito B, Matsumoto S, Okaniwa M, Ambrus-Aikelin G, Morishita D, Kitazawa S, Uchiyama N, Ogawa K, Kimura H, Imamura S J Med Chem. 2020 Mar 26;63(6):3215-3226. doi: 10.1021/acs.jmedchem.9b01979. Epub , 2020 Mar 16. PMID:32142284<ref>PMID:32142284</ref>
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Description: 1.65 Angstrom ternary complex of Deoxyhypusine synthase with cofactor NAD and spermidine mimic inhibitor GC7
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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: Ambrus-Aikelin, G]]
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<div class="pdbe-citations 6p4v" style="background-color:#fffaf0;"></div>
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[[Category: Klein, M.G]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ambrus-Aikelin G]]
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[[Category: Klein MG]]

Current revision

1.65 Angstrom ternary complex of Deoxyhypusine synthase with cofactor NAD and spermidine mimic inhibitor GC7

PDB ID 6p4v

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