Dual specificity tyrosine-phosphorylation-regulated kinase
From Proteopedia
(Difference between revisions)
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<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
| - | the article describing Jmol <ref>PMID:21638687</ref> to the rescue. | ||
== Function == | == Function == | ||
| - | '''Dual specificity tyrosine-phosphorylation-regulated kinase''' (DYRK) | + | '''Dual specificity tyrosine-phosphorylation-regulated kinase''' (DYRK) is a member of a 5-member family of evolutionary conserved protein kinases. '''DYRK1A''' is associated with both neuropathological phenotypes and cancer susceptibility in patients with Down syndrome<ref>PMID:29985601</ref>. '''DYRK2''' is a 26S proteasome-regulating kinase. |
== Disease == | == Disease == | ||
== Relevance == | == Relevance == | ||
| + | |||
| + | DYRK1A protects against insulin resistance in the brain by elevating insulin receptor substrate 1 expression<ref>PMID:31723029</ref>. DYRK1A inhibitors attenuate cognitive dysfunction in animal models for Down syndrome and Alzheimer Disease. DYRK1A is a potential cancer therapeutic target because of its role in the regulation of cell cycle progression by affecting both tumor suppressors and oncogenes. Some DYRK1A inhibitors block the tau phosphorylation that is a hallmark of Alzheimer's disease<ref>PMID:30095246</ref>. DYRK2 is a therapeutic target for multiple myeloma and triple-negative breast cancer<ref>PMID:31754034</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
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**[[4nct]] - hDYRK kinase domain + phosphoTyr + phophoSer + inhibitor - human<br /> | **[[4nct]] - hDYRK kinase domain + phosphoTyr + phophoSer + inhibitor - human<br /> | ||
| - | **[[6eij]], [[6eiq]], [[6eil]], [[6eip]], [[6eif]], [[6eis]], [[6ej4]], [[6eir]], [[6eiv]], [[2vx3]], [[5a4l]], [[5a4t]], [[6eil]], [[6s14]], [[6s1l]], [[6s1b]], [[6s1i]], [[6s1j]], [[6s17]], [[3anq]], [[4ylj]], [[4ylk]], [[4yll]], [[5a3x]], [[5a4e]], [[5a4q]], [[5a54]], [[4mq1]], [[4mq2]], [[6uip]], [[6a1g]], [[6a1f]], [[6t6a]] - hDYRK kinase domain + phosphoTyr + inhibitor<br /> | + | **[[6eij]], [[6eiq]], [[6eil]], [[6eip]], [[6eif]], [[6eis]], [[6ej4]], [[6eir]], [[6eiv]], [[2vx3]], [[5a4l]], [[5a4t]], [[6eil]], [[6s14]], [[6s1l]], [[6s1b]], [[6s1i]], [[6s1j]], [[6s17]], [[3anq]], [[4ylj]], [[4ylk]], [[4yll]], [[5a3x]], [[5a4e]], [[5a4q]], [[5a54]], [[4mq1]], [[4mq2]], [[6uip]], [[6a1g]], [[6a1f]], [[6t6a]], [[6qu2]] - hDYRK kinase domain + phosphoTyr + inhibitor<br /> |
**[[5aik]] - hDYRK kinase domain + phosphoTyr + inhibitor + phosphate<br /> | **[[5aik]] - hDYRK kinase domain + phosphoTyr + inhibitor + phosphate<br /> | ||
**[[3anr]], [[4yu2]] - hDYRK kinase domain + phosphoTyr + harmine derivative<br /> | **[[3anr]], [[4yu2]] - hDYRK kinase domain + phosphoTyr + harmine derivative<br /> | ||
Revision as of 09:24, 19 April 2020
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3D structures of dual specificity tyrosine-phosphorylation-regulated kinase
References
- ↑ Jarhad DB, Mashelkar KK, Kim HR, Noh M, Jeong LS. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Inhibitors as Potential Therapeutics. J Med Chem. 2018 Nov 21;61(22):9791-9810. doi: 10.1021/acs.jmedchem.8b00185. Epub, 2018 Jul 20. PMID:29985601 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b00185
- ↑ Tian S, Jia W, Lu M, Zhao J, Sun X. Dual-specificity tyrosine phosphorylation-regulated kinase 1A ameliorates insulin resistance in neurons by up-regulating IRS-1 expression. J Biol Chem. 2019 Dec 27;294(52):20164-20176. doi: 10.1074/jbc.RA119.010809. Epub, 2019 Nov 13. PMID:31723029 doi:http://dx.doi.org/10.1074/jbc.RA119.010809
- ↑ Czarna A, Wang J, Zelencova D, Liu Y, Deng X, Choi HG, Zhang T, Zhou W, Chang JW, Kildalsen H, Seternes OM, Gray NS, Engh RA, Rothweiler U. Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors. J Med Chem. 2018 Aug 23. doi: 10.1021/acs.jmedchem.7b01847. PMID:30095246 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b01847
- ↑ Banerjee S, Wei T, Wang J, Lee JJ, Gutierrez HL, Chapman O, Wiley SE, Mayfield JE, Tandon V, Juarez EF, Chavez L, Liang R, Sah RL, Costello C, Mesirov JP, de la Vega L, Cooper KL, Dixon JE, Xiao J, Lei X. Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression. Proc Natl Acad Sci U S A. 2019 Nov 21. pii: 1912033116. doi:, 10.1073/pnas.1912033116. PMID:31754034 doi:http://dx.doi.org/10.1073/pnas.1912033116
