4jht
From Proteopedia
(Difference between revisions)
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==Crystal Structure of AlkB in complex with 5-carboxy-8-hydroxyquinoline (IOX1)== | ==Crystal Structure of AlkB in complex with 5-carboxy-8-hydroxyquinoline (IOX1)== | ||
| - | <StructureSection load='4jht' size='340' side='right' caption='[[4jht]], [[Resolution|resolution]] 1.18Å' scene=''> | + | <StructureSection load='4jht' size='340' side='right'caption='[[4jht]], [[Resolution|resolution]] 1.18Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4jht]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JHT FirstGlance]. <br> | <table><tr><td colspan='2'>[[4jht]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JHT FirstGlance]. <br> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref> | [[http://www.uniprot.org/uniprot/ALKB_ECOLI ALKB_ECOLI]] Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).<ref>PMID:12226668</ref> <ref>PMID:12594517</ref> <ref>PMID:16482161</ref> <ref>PMID:19706517</ref> <ref>PMID:21068844</ref> <ref>PMID:20084272</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 2-Oxoglutarate and iron dependent oxygenases are therapeutic targets for human diseases. Using a representative 2OG oxygenase panel, we compare the inhibitory activities of 5-carboxy-8-hydroxyquinoline (IOX1) and 4-carboxy-8-hydroxyquinoline (4C8HQ) with that of two other commonly used 2OG oxygenase inhibitors, N-oxalylglycine (NOG) and 2,4-pyridinedicarboxylic acid (2,4-PDCA). The results reveal that IOX1 has a broad spectrum of activity, as demonstrated by the inhibition of transcription factor hydroxylases, representatives of all 2OG dependent histone demethylase subfamilies, nucleic acid demethylases and gamma-butyrobetaine hydroxylase. Cellular assays show that, unlike NOG and 2,4-PDCA, IOX1 is active against both cytosolic and nuclear 2OG oxygenases without ester derivatisation. Unexpectedly, crystallographic studies on these oxygenases demonstrate that IOX1, but not 4C8HQ, can cause translocation of the active site metal, revealing a rare example of protein ligand-induced metal movement. | ||
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| + | 5-Carboxy-8-hydroxyquinoline is a Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor which Causes Iron Translocation.,Hopkinson RJ, Tumber A, Yapp C, Chowdhury R, Aik W, Che KH, Li XS, Kristensen JBL, King ONF, Chan MC, Yeoh KK, Choi H, Walport LJ, Thinnes CC, Bush JT, Lejeune C, Rydzik AM, Rose NR, Bagg EA, McDonough MA, Krojer T, Yue WW, Ng SS, Olsen L, Brennan PE, Oppermann U, Muller-Knapp S, Klose RJ, Ratcliffe PJ, Schofield CJ, Kawamura A Chem Sci. 2013 Aug 1;4(8):3110-3117. doi: 10.1039/C3SC51122G. PMID:26682036<ref>PMID:26682036</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4jht" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: DNA oxidative demethylase]] | [[Category: DNA oxidative demethylase]] | ||
[[Category: Ecoli]] | [[Category: Ecoli]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Aik, W S]] | [[Category: Aik, W S]] | ||
[[Category: McDonough, M A]] | [[Category: McDonough, M A]] | ||
Revision as of 10:02, 25 December 2019
Crystal Structure of AlkB in complex with 5-carboxy-8-hydroxyquinoline (IOX1)
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