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PDBsum entry 1cxp
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Oxidoreductase
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PDB id
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1cxp
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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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X-Ray crystal structure and characterization of halide-Binding sites of human myeloperoxidase at 1.8 a resolution.
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Authors
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T.J.Fiedler,
C.A.Davey,
R.E.Fenna.
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Ref.
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J Biol Chem, 2000,
275,
11964-11971.
[DOI no: ]
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PubMed id
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Abstract
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The x-ray crystal structure of human myeloperoxidase has been extended to 1.8 A
resolution, using x-ray data recorded at -180 degrees C (r = 0.197, free r =
0.239). Results confirm that the heme is covalently attached to the protein via
two ester linkages between the carboxyl groups of Glu(242) and Asp(94) and
modified methyl groups on pyrrole rings A and C of the heme as well as a
sulfonium ion linkage between the sulfur atom of Met(243) and the beta-carbon of
the vinyl group on pyrrole ring A. In the native enzyme a bound chloride ion has
been identified at the amino terminus of the helix containing the proximal
His(336). Determination of the x-ray crystal structure of a
myeloperoxidase-bromide complex (r = 0.243, free r = 0.296) has shown that this
chloride ion can be replaced by bromide. Bromide is also seen to bind, at
partial occupancy, in the distal heme cavity, in close proximity to the distal
His(95), where it replaces the water molecule hydrogen bonded to Gln(91). The
bromide-binding site in the distal cavity appears to be the halide-binding site
responsible for shifts in the Soret band of the absorption spectrum of
myeloperoxidase. It is proposed that halide binding to this site inhibits the
enzyme by effectively competing with H(2)O(2) for access to the distal
histidine, whereas in compound I, the same site may be the halide
substrate-binding site.
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Figure 3.
Fig. 3. Stereo view of the hydrogen bonding pattern for
the five water molecules (W1-W5) inside the distal cavity.
Superimposed is the F[o]  F[c]
bromide difference map contoured at ±4  , showing
additional density at W2 corresponding to partial substitution
by bromide. Small negative and larger positive features indicate
a slight shift in the iron position.
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Figure 5.
Fig. 5. Stereo view of the proximal helix
chloride-binding site in the native MPO model. Residues 324-327
at the carboxyl terminus of the proximal helix are linked to
residues 30-33 via two main chain hydrogen bonds. Superimposed
is the F[o] F[c]
bromide difference map contoured at 5 and 15 , showing
additional density corresponding to replacement of chloride by
bromide.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
11964-11971)
copyright 2000.
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Secondary reference #1
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Title
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Structure of the green heme in myeloperoxidase.
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Authors
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R.Fenna,
J.Zeng,
C.Davey.
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Ref.
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Arch Biochem Biophys, 1995,
316,
653-656.
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PubMed id
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Secondary reference #2
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Title
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2.3 a resolution X-Ray crystal structure of the bisubstrate analogue inhibitor salicylhydroxamic acid bound to human myeloperoxidase: a model for a prereaction complex with hydrogen peroxide.
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Authors
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C.A.Davey,
R.E.Fenna.
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Ref.
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Biochemistry, 1996,
35,
10967-10973.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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X-Ray crystal structure of canine myeloperoxidase at 3 a resolution.
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Authors
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J.Zeng,
R.E.Fenna.
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Ref.
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J Mol Biol, 1992,
226,
185-207.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2. Stereo photograph showing te averaged electron density ma on the proximal side of the heme. Residues
R333, Y334 G335, H336, T337, L338 and 1339 are located in helix H8 and include histidine 336, which provides the
proximal ligand to the heme iron. The carboxl group of glutamate 242 can be .seen to occupy electron density that is
continuous-with that of the heme macrocycle
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Figure 4.
Figure 4. tereo photograph of the averaged electon density map corresponding to the first 2 N-acetylglucosamine
(NAG) residues attached to Asn317. The orientations f both sugar molecules are clearly defined by density
corresponding to the N-acetyl groups. From the C5 position of the 1st sugr, electron density (not shown) corresponding
to t,he l-6 linked fucose projcts backwards.
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The above figures are
reproduced from the cited reference
with permission from Elsevier
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Secondary reference #4
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Title
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Site-Directed mutagenesis of human myeloperoxidase: further identification of residues involved in catalytic activity and heme interaction.
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Authors
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A.Jacquet,
L.Garcia-Quintana,
V.Deleersnyder,
R.Fenna,
A.Bollen,
N.Moguilevsky.
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Ref.
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Biochem Biophys Res Commun, 1994,
202,
73-81.
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PubMed id
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