6a1f: Difference between revisions
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==Crystal structure of human DYRK1A in complex with compound 14== | ==Crystal structure of human DYRK1A in complex with compound 14== | ||
<StructureSection load='6a1f' size='340' side='right' caption='[[6a1f]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='6a1f' size='340' side='right'caption='[[6a1f]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6a1f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6A1F OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6a1f]] is a 1 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=6A1F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6A1F FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9OF:8-methoxy-5,5-dimethyl-6~{H}-benzo[h]quinazolin-4-amine'>9OF</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6a1f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6a1f OCA], [https://pdbe.org/6a1f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6a1f RCSB], [https://www.ebi.ac.uk/pdbsum/6a1f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6a1f ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:[https://omim.org/entry/614104 614104]. A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21294719</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/DYR1A_HUMAN DYR1A_HUMAN] May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.<ref>PMID:8769099</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 26: | Line 25: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Baba D]] | ||
[[Category: | [[Category: Hanzawa H]] | ||
Latest revision as of 10:48, 17 October 2024
Crystal structure of human DYRK1A in complex with compound 14Crystal structure of human DYRK1A in complex with compound 14
Structural highlights
DiseaseDYR1A_HUMAN Defects in DYRK1A are the cause of mental retardation autosomal dominant type 7 (MRD7) [MIM:614104. A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.[1] FunctionDYR1A_HUMAN May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates.[2] Publication Abstract from PubMedHepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure-activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation. Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives.,Fukuda T, Ishiyama T, Katagiri T, Ueda K, Muramatsu S, Hashimoto M, Aki A, Baba D, Watanabe K, Tanaka N Bioorg Med Chem Lett. 2018 Sep 8. pii: S0960-894X(18)30741-8. doi:, 10.1016/j.bmcl.2018.09.010. PMID:30217414[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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