2iuw
From Proteopedia
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| - | [[Image:2iuw.gif|left|200px]]<br /> | + | [[Image:2iuw.gif|left|200px]]<br /><applet load="2iuw" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2iuw" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="2iuw, resolution 1.50Å" /> | caption="2iuw, resolution 1.50Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN ABH3 IN COMPLEX WITH IRON ION AND 2-OXOGLUTARATE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2IUW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FE, AKG and BME as [http://en.wikipedia.org/wiki/ligands ligands]. | + | 2IUW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FE, AKG and BME as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:Bme Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IUW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: polymorphism]] | [[Category: polymorphism]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 19:35:38 2007'' |
Revision as of 17:25, 18 December 2007
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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 with FE, AKG and BME as ligands. Known structural/functional Site: . 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 Tue Dec 18 19:35:38 2007
Categories: Homo sapiens | Single protein | Aas, P.A. | Bjoras, M. | Desousa, M.M.L. | Drablos, F. | Krokan, H.E. | Slupphaug, G. | Sundheim, O. | Tainer, J.A. | Talstad, V. | Vagbo, C.B. | AKG | BME | FE | Beta jellyroll | Demethylase | Dna/rna repair | Fe/2og-dependent dioxygenase | Mad | Oxidoreductase | Polymorphism
