View source for 7ckk


==Structural complex of FTO bound with Dac51==
<StructureSection load='7ckk' size='340' side='right'caption='[[7ckk]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ckk]] 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=7CKK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CKK 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B6C:2-{[2,6-dichloro-4-(3,5-dimethyl-1H-pyrazol-4-yl)phenyl]amino}-N-hydroxybenzamide'>B6C</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</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=7ckk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ckk OCA], [https://pdbe.org/7ckk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ckk RCSB], [https://www.ebi.ac.uk/pdbsum/7ckk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ckk ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM:[https://omim.org/entry/612938 612938]. A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years.<ref>PMID:19559399</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FTO_HUMAN FTO_HUMAN] Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation.<ref>PMID:18775698</ref> <ref>PMID:20376003</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The ever-increasing understanding of the complexity of factors and regulatory layers that contribute to immune evasion facilitates the development of immunotherapies. However, the diversity of malignant tumors limits many known mechanisms in specific genetic and epigenetic contexts, manifesting the need to discover general driver genes. Here, we have identified the m(6)A demethylase FTO as an essential epitranscriptomic regulator utilized by tumors to escape immune surveillance through regulation of glycolytic metabolism. We show that FTO-mediated m(6)A demethylation in tumor cells elevates the transcription factors c-Jun, JunB, and C/EBPbeta, which allows the rewiring of glycolytic metabolism. Fto knockdown impairs the glycolytic activity of tumor cells, which restores the function of CD8(+) T cells, thereby inhibiting tumor growth. Furthermore, we developed a small-molecule compound, Dac51, that can inhibit the activity of FTO, block FTO-mediated immune evasion, and synergize with checkpoint blockade for better tumor control, suggesting reprogramming RNA epitranscriptome as a potential strategy for immunotherapy.

Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance.,Liu Y, Liang G, Xu H, Dong W, Dong Z, Qiu Z, Zhang Z, Li F, Huang Y, Li Y, Wu J, Yin S, Zhang Y, Guo P, Liu J, Xi JJ, Jiang P, Han D, Yang CG, Xu MM Cell Metab. 2021 Jun 1;33(6):1221-1233.e11. doi: 10.1016/j.cmet.2021.04.001. Epub, 2021 Apr 27. PMID:33910046<ref>PMID:33910046</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ckk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gan J]]
[[Category: Yang C]]