View source for 5mkv


==Crystal Structure of Human Dihydropyrimidinease-like 2 (DPYSL2A)/Collapsin Response Mediator Protein (CRMP2) residues 13-516==
<StructureSection load='5mkv' size='340' side='right'caption='[[5mkv]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mkv]] is a 4 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=5MKV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MKV 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5mkv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mkv OCA], [https://pdbe.org/5mkv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mkv RCSB], [https://www.ebi.ac.uk/pdbsum/5mkv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mkv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPYL2_HUMAN DPYL2_HUMAN] Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.<ref>PMID:11477421</ref> <ref>PMID:15466863</ref> 
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== Publication Abstract from PubMed ==
Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy.

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.,Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC Jr., Sood AK, von Delft F, Ahmed AA Nat Commun. 2018 Feb 2;9(1):476. doi: 10.1038/s41467-017-02811-7. PMID:29396402<ref>PMID:29396402</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mkv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ahmed AA]]
[[Category: Arrowsmith CH]]
[[Category: Bountra C]]
[[Category: Edwards AM]]
[[Category: Krojer T]]
[[Category: Sethi R]]
[[Category: Velupillai S]]
[[Category: Zheng Y]]
[[Category: Von Delft F]]