View source for 4zbn


==Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor==
<StructureSection load='4zbn' size='340' side='right'caption='[[4zbn]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zbn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=4ZBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZBN 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]] 2.447&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUZ:5-(BENZYLCARBAMOYL)-2-DEOXYURIDINE+5-(DIHYDROGEN+PHOSPHATE)'>DUZ</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=4zbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zbn OCA], [https://pdbe.org/4zbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zbn RCSB], [https://www.ebi.ac.uk/pdbsum/4zbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zbn ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN] Defects in NGF are the cause of hereditary sensory and autonomic neuropathy type 5 (HSAN5) [MIM:[https://omim.org/entry/608654 608654]. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable.<ref>PMID:14976160</ref> <ref>PMID:20978020</ref> <ref>PMID:22302274</ref> 
== Function ==
[https://www.uniprot.org/uniprot/NGF_HUMAN NGF_HUMAN] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival.
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== Publication Abstract from PubMed ==
Discerning the structural building blocks of macromolecules is essential for understanding their folding and function. For a new generation of modified nucleic acid ligands (called slow off-rate modified aptamers or SOMAmers), we previously observed essential functions of hydrophobic aromatic side chains in the context of well-known nucleic acid motifs. Here we report a 2.45-A resolution crystal structure of a SOMAmer complexed with nerve growth factor that lacks any known nucleic acid motifs, instead adopting a configuration akin to a triangular prism. The SOMAmer utilizes extensive hydrophobic stacking interactions, non-canonical base pairing and irregular purine glycosidic bond angles to adopt a completely non-helical, compact S-shaped structure. Aromatic side chains contribute to folding by creating an unprecedented intercalating zipper-like motif and a prominent hydrophobic core. The structure provides compelling rationale for potent inhibitory activity of the SOMAmer and adds entirely novel motifs to the repertoire of structural elements uniquely available to SOMAmers.

Non-helical DNA Triplex Forms a Unique Aptamer Scaffold for High Affinity Recognition of Nerve Growth Factor.,Jarvis TC, Davies DR, Hisaminato A, Resnicow DI, Gupta S, Waugh SM, Nagabukuro A, Wadatsu T, Hishigaki H, Gawande B, Zhang C, Wolk SK, Mayfield WS, Nakaishi Y, Burgin AB, Stewart LJ, Edwards TE, Gelinas AD, Schneider DJ, Janjic N Structure. 2015 May 13. pii: S0969-2126(15)00145-8. doi:, 10.1016/j.str.2015.03.027. PMID:26027732<ref>PMID:26027732</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4zbn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Nerve growth factor|Nerve growth factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Davies DR]]
[[Category: Edwards TE]]