5f8p: Difference between revisions

Latest revision as of 06:42, 19 July 2023

A Novel Inhibitor of the Obesity-Related Protein FTO

Structural highlights

5f8p is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:	AKG, FE2, FIJ, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

↑ 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
↑ 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
↑ 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

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OCA

[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

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='5f8p' size='340' side='right'caption='[[5f8p]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5f8p]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F8P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F8P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5f8p]] 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=5F8P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F8P FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=FIJ:4-CHLORANYL-6-[(2~{S})-6-CHLORANYL-2,4,4-TRIMETHYL-7-OXIDANYL-3~{H}-CHROMEN-2-YL]BENZENE-1,3-DIOL'>FIJ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FTO, KIAA1752 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKG:2-OXOGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=FIJ:4-CHLORANYL-6-[(2~{S})-6-CHLORANYL-2,4,4-TRIMETHYL-7-OXIDANYL-3~{H}-CHROMEN-2-YL]BENZENE-1,3-DIOL'>FIJ</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'>[http://proteopedia.org/fgij/fg.htm?mol=5f8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f8p OCA], [http://pdbe.org/5f8p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f8p RCSB], [http://www.ebi.ac.uk/pdbsum/5f8p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f8p ProSAT]</span></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=5f8p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f8p OCA], [https://pdbe.org/5f8p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f8p RCSB], [https://www.ebi.ac.uk/pdbsum/5f8p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f8p ProSAT]</span></td></tr>
 </table>
 == 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>
+[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 ==
-[[http://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>
+[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>
 ==See Also==
@@ Line 19: / Line 19: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chai, J]]
+[[Category: Chai J]]
-[[Category: Han, Z]]
+[[Category: Han Z]]
-[[Category: Liu, W]]
+[[Category: Liu W]]
-[[Category: Zhou, B]]
+[[Category: Zhou B]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
-[[Category: Small molecule]]

5f8p: Difference between revisions

Latest revision as of 06:42, 19 July 2023

A Novel Inhibitor of the Obesity-Related Protein FTO

Structural highlights

Disease

Function

See Also

References

Contents

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