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PDBsum entry 1tkl
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Oxidoreductase
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PDB id
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1tkl
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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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Crystal structure of the oxygen-Dependant coproporphyrinogen oxidase (hem13p) of saccharomyces cerevisiae.
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Authors
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J.D.Phillips,
F.G.Whitby,
C.A.Warby,
P.Labbe,
C.Yang,
J.W.Pflugrath,
J.D.Ferrara,
H.Robinson,
J.P.Kushner,
C.P.Hill.
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Ref.
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J Biol Chem, 2004,
279,
38960-38968.
[DOI no: ]
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PubMed id
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Abstract
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Coproporphyrinogen oxidase (CPO) is an essential enzyme that catalyzes the sixth
step of the heme biosynthetic pathway. Unusually for heme biosynthetic enzymes,
CPO exists in two evolutionarily and mechanistically distinct families, with
eukaryotes and some prokaryotes employing members of the highly conserved
oxygen-dependent CPO family. Here, we report the crystal structure of the
oxygen-dependent CPO from Saccharomyces cerevisiae (Hem13p), which was
determined by optimized sulfur anomalous scattering and refined to a resolution
of 2.0 A. The protein adopts a novel structure that is quite different from
predicted models and features a central flat seven-stranded anti-parallel sheet
that is flanked by helices. The dimeric assembly, which is seen in different
crystal forms, is formed by packing of helices and a short isolated strand that
forms a beta-ladder with its counterpart in the partner subunit. The deep
active-site cleft is lined by conserved residues and has been captured in open
and closed conformations in two different crystal forms. A substratesized cavity
is completely buried in the closed conformation by the approximately 8-A
movement of a helix that forms a lid over the active site. The structure
therefore suggests residues that likely play critical roles in catalysis and
explains the deleterious effect of many of the mutations associated with the
disease hereditary coproporphyria.
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Figure 1.
FIG. 1. Schematic of reaction catalyzed by odCPO/Hem13p.
Propionate side chains on the pyrrole A and B rings are
decarboxylated to form vinyl groups and two molecules of carbon
dioxide. Molecular oxygen is converted to hydrogen peroxide,
presumably via abstraction of a hydrogen atom from each of the
propionate/vinyl C-  atoms.
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Figure 6.
FIG. 6. Locations of mutations identified in coproporphyria
patients. Shown is a worm representation stereo view of form II
(closed) structure in the same orientation as shown in Fig. 3A.
Sites of mutations identified in patients are shown as spheres.
Substitutions expected to destabilize the folded protein
structure are shown in gray. Mutations whose presumed
deleterious effect is not easily explained by the structure are
shown in blue. Mutations at the active-site cleft are shown in
magenta. The modeled substrate molecule (white) indicates the
approximate location of the active-site cavity.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
38960-38968)
copyright 2004.
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