4cxx: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4cxx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CXX FirstGlance]. <br>
<table><tr><td colspan='2'>[[4cxx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CXX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CXX FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=640:4-(2-{[4-(4-TERT-BUTYLBENZYL)PYRIDIN-3-YL]CARBONYL}HYDRAZINYL)-4-OXOBUTANOIC+ACID'>640</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene><br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=640:(2E)-4-{N-[4-(4-TERT-BUTYL-BENZYL)-PYRIDINE-3-CARBONYL]-HYDRAZINO}-4-OXO-BUT-2-ENOIC+ACID'>640</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cxw|4cxw]], [[4cxy|4cxy]], [[4cxz|4cxz]], [[4cy0|4cy0]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cxw|4cxw]], [[4cxy|4cxy]], [[4cxz|4cxz]], [[4cy0|4cy0]]</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cxx RCSB], [http://www.ebi.ac.uk/pdbsum/4cxx PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cxx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cxx RCSB], [http://www.ebi.ac.uk/pdbsum/4cxx PDBsum]</span></td></tr>
<table>
</table>
== Disease ==
== Disease ==
[[http://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:[http://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>   
[[http://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:[http://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>   

Revision as of 08:58, 8 October 2014

Crystal structure of human FTO in complex with acylhydrazine inhibitor 16Crystal structure of human FTO in complex with acylhydrazine inhibitor 16

Structural highlights

4cxx is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[FTO_HUMAN] Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (GDFD) [MIM: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.[1]

Function

[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.[2] [3]

References

  1. ↑ Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O'Rahilly S, Munnich A, Colleaux L. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet. 2009 Jul;85(1):106-11. doi: 10.1016/j.ajhg.2009.06.002. Epub 2009, Jun 25. PMID:19559399 doi:10.1016/j.ajhg.2009.06.002
  2. ↑ Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 2008 Oct 15;582(23-24):3313-9. doi: 10.1016/j.febslet.2008.08.019., Epub 2008 Sep 5. PMID:18775698 doi:10.1016/j.febslet.2008.08.019
  3. ↑ Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J. Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature. 2010 Apr 22;464(7292):1205-9. Epub 2010 Apr 7. PMID:20376003 doi:10.1038/nature08921

4cxx, resolution 2.76Å

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