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Function
Fascin (FASC) is an actin microfilament cross-linking and bundling protein in mammalian cells. At least 3 fascins are known. FASC 1 is expressed in multiple cells while FASC 2 is found mostly in retina and FASC 3 in testis[1].
Disease
There is a direct relation between FASC expression in breast cancer patients and metastasis and shorter disease-free
survival[2].
Relevance
FASC is overexpresed in inflammatory bowel disease[3].
Structural highlights
FASC 3D structure shows it to contain 4 β-trefoil domains. A complex between FASC and an anti-metastatic agent shows the inhibitor binding to domains 1 and 2 [4]. The anti-metastatic agent is situated in deep pocket.
- ↑ Gungor-Ordueri NE, Cheng CY. Fascin - An actin binding and bundling protein in the testis and its role in ectoplasmic specialization dynamics. Spermatogenesis. 2015 Feb 23;5(1):e1002733. doi: 10.1080/21565562.2014.1002733., eCollection 2015 Jan-Apr. PMID:26413410 doi:https://dx.doi.org/10.1080/21565562.2014.1002733
- ↑ Al-Alwan M, Olabi S, Ghebeh H, Barhoush E, Tulbah A, Al-Tweigeri T, Ajarim D, Adra C. Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS One. 2011;6(11):e27339. doi: 10.1371/journal.pone.0027339. Epub 2011 Nov 4. PMID:22076152 doi:https://dx.doi.org/10.1371/journal.pone.0027339
- ↑ Qualtrough D, Smallwood K, Littlejohns D, Pignatelli M. The actin-bundling protein fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair. BMC Gastroenterol. 2011 Feb 23;11:14. doi: 10.1186/1471-230X-11-14. PMID:21345224 doi:https://dx.doi.org/10.1186/1471-230X-11-14
- ↑ Francis S, Croft D, Schuttelkopf AW, Parry C, Pugliese A, Cameron K, Claydon S, Drysdale M, Gardner C, Gohlke A, Goodwin G, Gray CH, Konczal J, McDonald L, Mezna M, Pannifer A, Paul NR, Machesky L, McKinnon H, Bower J. Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents. Bioorg Med Chem Lett. 2019 Jan 30. pii: S0960-894X(19)30056-3. doi:, 10.1016/j.bmcl.2019.01.035. PMID:30773430 doi:https://dx.doi.org/10.1016/j.bmcl.2019.01.035
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3D structures of fascin
1dfc, 3llp, 3p53 - hFASC 1 - human
4gov, 4goy, 4gp0, 4gp3 - hFASC 1 (mutant)
6i0z, 6i17, 6i16, 6i18, 6i11, 6i10, 6i13, 6i12, 6i15, 6i14 - hFASC + anti-metastatic inhibitor
6b0t - hFASC + inhibitor
8vo6, 8vo7, 8vo8, 8vo9, 8voa – hFASC + actin – Cryo EM
7zau – hFASC + nanobody
References
