View source for 2fdj

[[Image:2fdj.gif|left|200px]]<br /><applet load="2fdj" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2fdj, resolution 2.100&Aring;" />
'''Crystal Structure of AlkB in complex with Fe(II) and succinate'''<br />

==Overview==
Nucleic acid damage by environmental and endogenous alkylation reagents, creates lesions that are both mutagenic and cytotoxic, with the latter, effect accounting for their widespread use in clinical cancer, chemotherapy. Escherichia coli AlkB and the homologous human proteins ABH2, and ABH3 (refs 5, 7) promiscuously repair DNA and RNA bases damaged by, S(N)2 alkylation reagents, which attach hydrocarbons to endocyclic ring, nitrogen atoms (N1 of adenine and guanine and N3 of thymine and cytosine)., Although the role of AlkB in DNA repair has long been established based on, phenotypic studies, its exact biochemical activity was only elucidated, recently after sequence profile analysis revealed it to be a member of the, Fe-oxoglutarate-dependent dioxygenase superfamily. These enzymes use an, Fe(II) cofactor and 2-oxoglutarate co-substrate to oxidize organic, substrates. AlkB hydroxylates an alkylated nucleotide base to produce an, unstable product that releases an aldehyde to regenerate the unmodified, base. Here we have determined crystal structures of substrate and product, complexes of E. coli AlkB at resolutions from 1.8 to 2.3 A. Whereas the, Fe-2-oxoglutarate dioxygenase core matches that in other superfamily, members, a unique subdomain holds a methylated trinucleotide substrate, into the active site through contacts to the polynucleotide backbone., Amide hydrogen exchange studies and crystallographic analyses suggest that, this substrate-binding 'lid' is conformationally flexible, which may, enable docking of diverse alkylated nucleotide substrates in optimal, catalytic geometry. Different crystal structures show open and closed, states of a tunnel putatively gating O2 diffusion into the active site., Exposing crystals of the anaerobic Michaelis complex to air yields slow, but substantial oxidation of 2-oxoglutarate that is inefficiently coupled, to nucleotide oxidation. These observations suggest that protein dynamics, modulate redox chemistry and that a hypothesized migration of the reactive, oxy-ferryl ligand on the catalytic Fe ion may be impeded when the protein, is constrained in the crystal lattice.

==About this Structure==
2FDJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with FE2 and SIN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FDJ OCA]. 

==Reference==
Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB., Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, Hunt JF, Nature. 2006 Feb 16;439(7078):879-84. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16482161 16482161]
[[Category: Escherichia coli]]
[[Category: Single protein]]
[[Category: Benach, J.]]
[[Category: Edstrom, W.C.]]
[[Category: Gibney, B.R.]]
[[Category: Hunt, J.F.]]
[[Category: NESG, Northeast.Structural.Genomics.Consortium.]]
[[Category: Yu, B.]]
[[Category: FE2]]
[[Category: SIN]]
[[Category: beta jellyroll]]
[[Category: nesg]]
[[Category: northeast structural genomics consortium]]
[[Category: protein structure initiative]]
[[Category: psi]]
[[Category: structural genomics]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:29:55 2007''