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PDBsum entry 1sql
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Biosynthesis of tetrahydrofolate in plants: crystal structure of 7,8-Dihydroneopterin aldolase from arabidopsis thaliana reveals a novel adolase class.
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Authors
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S.Bauer,
A.K.Schott,
V.Illarionova,
A.Bacher,
R.Huber,
M.Fischer.
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Ref.
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J Mol Biol, 2004,
339,
967-979.
[DOI no: ]
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PubMed id
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Abstract
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Dihydroneopterin aldolase (DHNA) catalyses a retroaldol reaction yielding
6-hydroxymethyl-7,8-dihydropterin, a biosynthetic precursor of the vitamin,
tetrahydrofolate. The enzyme is a potential target for antimicrobial and
anti-parasite chemotherapy. A gene specifying a dihydroneopterin aldolase from
Arabidopsis thaliana was expressed in a recombinant Escherichia coli strain. The
recombinant protein was purified to apparent homogeneity and crystallised using
polyethylenglycol as the precipitating agent. The crystal structure was solved
by X-ray diffraction analysis at 2.2A resolution. The enzyme forms a
D(4)-symmetric homooctamer. Each polypeptide chain is folded into a single
domain comprising an antiparallel four-stranded beta-sheet and two long
alpha-helices. Four monomers are arranged in a tetrameric ring, and two of these
rings form a hollow cylinder. Well defined purine derivatives are found at all
eight topologically equivalent active sites. The subunit fold of the enzyme is
related to substructures of dihydroneopterin triphosphate epimerase, GTP
cyclohydrolase I, and pyruvoyltetrahydropterin synthase, which are all involved
in the biosynthesis of pteridine type cofactors, and to urate oxidase, although
some members of that superfamily have no detectable sequence similarity. Due to
structural and mechanistical differences of DHNA in comparison with class I and
class II aldolases, a new aldolase class is proposed.
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Figure 9.
Figure 9. Stereo drawing of the A. thaliana DHNA active
site with electron density for the bound guanine and the water
molecule. Residues that form hydrophobic or hydrogen bond
interactions are shown. Ser52 and Tyr53 belong to the adjacent
subunit. The final 2F[o] -F[c] electron density map covering the
ligand and the water molecule is contoured at 1 sigma.
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Figure 12.
Figure 12. Proposed catalytic mechanism of A. thaliana DHNA.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
339,
967-979)
copyright 2004.
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