2iuw

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{{STRUCTURE_2iuw| PDB=2iuw | SCENE= }}
{{STRUCTURE_2iuw| PDB=2iuw | SCENE= }}
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'''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''
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===CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 16858410 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16858410}}
==About this Structure==
==About this Structure==
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[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Polymorphism]]
[[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 Tue Jul 29 15:20:23 2008''

Revision as of 12:20, 29 July 2008

Image:2iuw.png

Template:STRUCTURE 2iuw

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

Template:ABSTRACT PUBMED 16858410

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

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