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PDBsum entry 1ah5
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References listed in PDB file
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Key reference
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Title
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Determination of the structure of seleno-Methionine-Labelled hydroxymethylbilane synthase in its active form by multi-Wavelength anomalous dispersion.
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Authors
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A.Hädener,
P.K.Matzinger,
A.R.Battersby,
S.Mcsweeney,
A.W.Thompson,
A.P.Hammersley,
S.J.Harrop,
A.Cassetta,
A.Deacon,
W.N.Hunter,
Y.P.Nieh,
J.Raftery,
N.Hunter,
J.R.Helliwell.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 1999,
55,
631-643.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
87%.
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Abstract
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The enzyme hydroxymethylbilane synthase (HMBS, E.C. 4.3.1.8) catalyzes the
conversion of porphobilinogen into hydroxymethylbilane, a key intermediate for
the biosynthesis of heme, chlorophylls, vitamin B12 and related macrocycles. The
enzyme is found in all organisms, except viruses. The crystal structure of the
selenomethionine-labelled enzyme ([SeMet]HMBS) from Escherichia coli has been
solved by the multi-wavelength anomalous dispersion (MAD) experimental method
using the Daresbury SRS station 9.5. In addition, [SeMet]HMBS has been studied
by MAD at the Grenoble ESRF MAD beamline BM14 (BL19) and this work is described
especially with respect to the use of the ESRF CCD detector. The structure at
ambient temperature has been refined, the R factor being 16.8% at 2. 4 A
resolution. The dipyrromethane cofactor of the enzyme is preserved in its
reduced form in the crystal and its geometrical shape is in full agreement with
the crystal structures of authentic dipyrromethanes. Proximal to the reactive C
atom of the reduced cofactor, spherical density is seen consistent with there
being a water molecule ideally placed to take part in the final step of the
enzyme reaction cycle. Intriguingly, the loop with residues 47-58 is not ordered
in the structure of this form of the enzyme, which carries no substrate. Direct
experimental study of the active enzyme is now feasible using time-resolved Laue
diffraction and freeze-trapping, building on the structural work described here
as the foundation.
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Figure 2.
Figure 2 Oxidation states of the cofactor of the HMBS
holoenzyme (R represents the apoenzyme moiety). (a)
Dipyrromethane structure (catalytically active); for labelling
conventions, see text; (b) dipyrromethene structure (inactive);
(c) dipyrromethenone structure (inactive). A = CH[2]COO^-; P =
CH[2]CH[2]COO^-.
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Figure 6.
Figure 6 Geometry of the reduced dipyrromethane cofactor. For
values of bond distances and bond angles, see Table 6-. (a)
Dipyrromethane core structure and thioether moiety used to
search the CSD; (b) atom names and bond types, and (c) angle
types used for the parameterization of the cofactor and the Cys
residue to which it is attached.
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The above figures are
reprinted
by permission from the IUCr:
Acta Crystallogr D Biol Crystallogr
(1999,
55,
631-643)
copyright 1999.
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