6oke

<table><tr><td colspan='2'>[[6oke]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Choanoflagellate Choanoflagellate]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OKE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OKE FirstGlance]. <br>

</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6okd|6okd]]</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oke OCA], [http://pdbe.org/6oke PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oke RCSB], [http://www.ebi.ac.uk/pdbsum/6oke PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oke ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

The impenetrability of the blood-brain barrier (BBB) to most conventional drugs impedes the treatment of central nervous system (CNS) disorders. Interventions for diseases like brain cancer, neurodegeneration, or age-associated inflammatory processes require varied approaches to CNS drug delivery. Of recent interest as drugs or drug-delivery vehicles are cystine-dense peptides (CDPs). Found throughout the phylogenetic tree, often in drug-like roles, their size, stability, and protein interaction capabilities make CDPs an attractive mid-size biologic scaffold to complement conventional antibody-based drugs. Here, we describe the identification, maturation, characterization, and utilization of a CDP that binds to the transferrin receptor (TfR), a native receptor and BBB transporter for the iron chaperone transferrin. We developed variants with varying binding affinities (KD as low as 216 pM), co-crystallized it with the receptor, and confirmed murine cross-reactivity. It accumulates in the mouse CNS at ~25% of blood levels (CNS blood content is only ~1-6%), and delivers neurotensin, an otherwise non-BBB-penetrant neuropeptide, at levels capable of modulating CREB signaling in the mouse brain. Our work highlights the utility of CDPs as a diverse, easy-to-screen scaffold family worthy of inclusion in modern drug discovery strategies, demonstrated by the discovery of a candidate CNS drug delivery vehicle ready for further optimization and preclinical development.

A TfR-Binding Cystine-Dense Peptide Promotes Blood-Brain Barrier Penetration of Bioactive Molecules.,Crook ZR, Girard E, Sevilla GP, Merrill M, Friend D, Rupert PB, Pakiam F, Nguyen E, Yin C, Ruff RO, Hopping G, Strand AD, Finton KAK, Coxon M, Mhyre AJ, Strong RK, Olson JM J Mol Biol. 2020 Apr 15. pii: S0022-2836(20)30279-5. doi:, 10.1016/j.jmb.2020.04.002. PMID:32304700<ref>PMID:32304700</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Choanoflagellate]]

[[Category: Rupert, P B]]

[[Category: Strong, R K]]

[[Category: Signaling protein]]