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PDBsum entry 1c9e
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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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Structural and mechanistic basis of porphyrin metallation by ferrochelatase.
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Authors
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D.Lecerof,
M.Fodje,
A.Hansson,
M.Hansson,
S.Al-Karadaghi.
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Ref.
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J Mol Biol, 2000,
297,
221-232.
[DOI no: ]
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PubMed id
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Abstract
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Ferrochelatase, the enzyme catalyzing metallation of protoporphyrin IX at the
terminal step of heme biosynthesis, was co-crystallized with an isomer mixture
of the potent inhibitor N-methylmesoporphyrin (N-MeMP). The X-ray structure
revealed the active site of the enzyme, to which only one of the isomers was
bound, and for the first time allowed characterization of the mode of porphyrin
macrocycle distortion by ferrochelatase. Crystallization of ferrochelatase and
N-MeMP in the presence of Cu(2+) leads to metallation and demethylation of
N-MeMP. A mechanism of porphyrin distortion is proposed, which assumes that the
enzyme holds pyrrole rings B, C and D in a vice-like grip and forces a 36
degrees tilt on ring A.
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Figure 5.
Figure 5. (a) A stereo view of N-MeMP bound to
ferrochelatase. The side-chains of amino acid residues in close
contact with the inhibitor are also shown. WAT represents a
solvent molecule coordinated to H183 and E264. This molecule may
easily be replaced by a metal ion at the first stage of the
enzymatic reaction. (b) A surface representation of the binding
pocket for N-MeMP. The red and blue colors correspond to
negative and positive surface potential, respectively. The
position of the tilted pyrrole ring A shows that any changes in
its conformation will result in steric clashes with protein
side-chains. The Figure was produced with the program GRASP
(Nicholls et al., 1991).
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Figure 7.
Figure 7. A stereo view of the structure of Cu:N-MeMP bound
in the active site of ferrochelatase superimposed on a composite
omit electron density map (blue). The density of the methyl
group in this case is much weaker than the corresponding density
in the N-MeMP complex (Figure 4). A difference (F[o] -F[c])
electron density for the Cu2+ contoured at 4s level is shown in
red.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
297,
221-232)
copyright 2000.
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