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PDBsum entry 1cmu
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Oxidoreductase (h2o2(a))
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PDB id
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1cmu
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Contents |
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* Residue conservation analysis
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Enzyme class:
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E.C.1.11.1.5
- cytochrome-c peroxidase.
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Reaction:
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2 Fe(II)-[cytochrome c] + H2O2 + 2 H+ = 2 Fe(III)-[cytochrome c] + 2 H2O
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2
×
Fe(II)-[cytochrome c]
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+
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H2O2
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+
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2
×
H(+)
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=
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2
×
Fe(III)-[cytochrome c]
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+
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2
×
H2O
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Cofactor:
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Heme
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Heme
Bound ligand (Het Group name =
HEM)
matches with 95.45% similarity
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Protein Sci
4:1844-1850
(1995)
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PubMed id:
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The role of aspartate-235 in the binding of cations to an artificial cavity at the radical site of cytochrome c peroxidase.
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M.M.Fitzgerald,
M.L.Trester,
G.M.Jensen,
D.E.McRee,
D.B.Goodin.
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ABSTRACT
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The activated state of cytochrome c peroxidase, compound ES, contains a cation
radical on the Trp-191 side chain. We recently reported that replacing this
tryptophan with glycine creates a buried cavity at the active site that contains
ordered solvent and that will specifically bind substituted imidazoles in their
protonated cationic forms (Fitzgerald MM, Churchill MJ, McRee DE, Goodin DB,
1994, Biochemistry 33:3807-3818). Proposals that a nearby carboxylate, Asp-235,
and competing monovalent cations should modulate the affinity of the W191G
cavity for ligand binding are addressed in this study. Competitive binding
titrations of the imidazolium ion to W191G as a function of [K+] show that
potassium competes weakly with the binding of imidazoles. The dissociation
constant observed for potassium binding (18 mM) is more than 3,000-fold higher
than that for 1,2-dimethylimidazole (5.5 microM) in the absence of competing
cations. Significantly, the W191G-D235N double mutant shows no evidence for
binding imidazoles in their cationic or neutral forms, even though the structure
of the cavity remains largely unperturbed by replacement of the carboxylate.
Refined crystallographic B-values of solvent positions indicate that the weakly
bound potassium in W191G is significantly depopulated in the double mutant.
These results demonstrate that the buried negative charge of Asp-235 is an
essential feature of the cation binding determinant and indicate that this
carboxylate plays a critical role in stabilizing the formation of the Trp-191
radical cation.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.M.Hays Putnam,
Y.T.Lee,
and
D.B.Goodin
(2009).
Replacement of an electron transfer pathway in cytochrome c peroxidase with a surrogate peptide.
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Biochemistry,
48,
1-3.
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PDB code:
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R.Baron,
and
J.A.McCammon
(2008).
(Thermo)dynamic role of receptor flexibility, entropy, and motional correlation in protein-ligand binding.
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Chemphyschem,
9,
983-988.
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R.E.Amaro,
R.Baron,
and
J.A.McCammon
(2008).
An improved relaxed complex scheme for receptor flexibility in computer-aided drug design.
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J Comput Aided Mol Des,
22,
693-705.
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A.M.Hays,
H.B.Gray,
and
D.B.Goodin
(2003).
Trapping of peptide-based surrogates in an artificially created channel of cytochrome c peroxidase.
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Protein Sci,
12,
278-287.
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R.J.Rosenfeld,
A.M.Hays,
R.A.Musah,
and
D.B.Goodin
(2002).
Excision of a proposed electron transfer pathway in cytochrome c peroxidase and its replacement by a ligand-binding channel.
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Protein Sci,
11,
1251-1259.
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PDB codes:
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J.Bujons,
A.Dikiy,
J.C.Ferrer,
L.Banci,
and
A.G.Mauk
(1997).
Charge reversal of a critical active-site residue of cytochrome-c peroxidase: characterization of the Arg48-->Glu variant.
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Eur J Biochem,
243,
72-84.
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R.A.Musah,
and
D.B.Goodin
(1997).
Introduction of novel substrate oxidation into cytochrome c peroxidase by cavity complementation: oxidation of 2-aminothiazole and covalent modification of the enzyme.
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Biochemistry,
36,
11665-11674.
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PDB code:
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C.A.Bonagura,
M.Sundaramoorthy,
H.S.Pappa,
W.R.Patterson,
and
T.L.Poulos
(1996).
An engineered cation site in cytochrome c peroxidase alters the reactivity of the redox active tryptophan.
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Biochemistry,
35,
6107-6115.
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M.M.Fitzgerald,
R.A.Musah,
D.E.McRee,
and
D.B.Goodin
(1996).
A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity.
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Nat Struct Biol,
3,
626-631.
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PDB codes:
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S.K.Wilcox,
G.M.Jensen,
M.M.Fitzgerald,
D.E.McRee,
and
D.B.Goodin
(1996).
Altering substrate specificity at the heme edge of cytochrome c peroxidase.
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Biochemistry,
35,
4858-4866.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
