2iuw

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[[Image:2iuw.gif|left|200px]]
[[Image:2iuw.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2iuw |SIZE=350|CAPTION= <scene name='initialview01'>2iuw</scene>, resolution 1.50&Aring;
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The line below this paragraph, containing "STRUCTURE_2iuw", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Bme+Binding+Site+For+Chain+A'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=AKG:2-OXYGLUTARIC+ACID'>AKG</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=LED:(4R)-5-OXO-L-LEUCINE'>LED</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_2iuw| PDB=2iuw | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iuw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iuw OCA], [http://www.ebi.ac.uk/pdbsum/2iuw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iuw RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''
'''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''
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[[Category: Talstad, V.]]
[[Category: Talstad, V.]]
[[Category: Vagbo, C B.]]
[[Category: Vagbo, C B.]]
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[[Category: beta jellyroll]]
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[[Category: Beta jellyroll]]
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[[Category: demethylase]]
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[[Category: Demethylase]]
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[[Category: dna/rna repair]]
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[[Category: Dna/rna repair]]
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[[Category: fe/2og-dependent dioxygenase]]
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[[Category: Fe/2og-dependent dioxygenase]]
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[[Category: mad]]
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[[Category: Mad]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:54:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:49:03 2008''
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Revision as of 04:54, 4 May 2008

Template:STRUCTURE 2iuw

CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE


Overview

Methylating agents are ubiquitous in the environment, and central in cancer therapy. The 1-methyladenine and 3-methylcytosine lesions in DNA/RNA contribute to the cytotoxicity of such agents. These lesions are directly reversed by ABH3 (hABH3) in humans and AlkB in Escherichia coli. Here, we report the structure of the hABH3 catalytic core in complex with iron and 2-oxoglutarate (2OG) at 1.5 A resolution and analyse key site-directed mutants. The hABH3 structure reveals the beta-strand jelly-roll fold that coordinates a catalytically active iron centre by a conserved His1-X-Asp/Glu-X(n)-His2 motif. This experimentally establishes hABH3 as a structural member of the Fe(II)/2OG-dependent dioxygenase superfamily, which couples substrate oxidation to conversion of 2OG into succinate and CO2. A positively charged DNA/RNA binding groove indicates a distinct nucleic acid binding conformation different from that predicted in the AlkB structure with three nucleotides. These results uncover previously unassigned key catalytic residues, identify a flexible hairpin involved in nucleotide flipping and ss/ds-DNA discrimination, and reveal self-hydroxylation of an active site leucine that may protect against uncoupled generation of dangerous oxygen radicals.

About this Structure

2IUW is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage., Sundheim O, Vagbo CB, Bjoras M, Sousa MM, Talstad V, Aas PA, Drablos F, Krokan HE, Tainer JA, Slupphaug G, EMBO J. 2006 Jul 26;25(14):3389-97. Epub 2006 Jul 6. PMID:16858410 Page seeded by OCA on Sun May 4 07:54:53 2008

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