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PDBsum entry 1jm0
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De novo protein
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PDB id
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1jm0
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DOI no:
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J Am Chem Soc
123:12749-12757
(2001)
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PubMed id:
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Toward the de novo design of a catalytically active helix bundle: a substrate-accessible carboxylate-bridged dinuclear metal center.
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L.Di Costanzo,
H.Wade,
S.Geremia,
L.Randaccio,
V.Pavone,
W.F.DeGrado,
A.Lombardi.
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ABSTRACT
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De novo design of proteins provides an attractive approach to uncover the
essential features required for their functions. Previously, we described the
design and crystal structure determination of a di-Zn(II) complex of
"due-ferri-1" (DF1), a protein patterned after the diiron-dimanganese class of
redox-active proteins [Lombardi, A.; Summa, C.; Geremia, S.; Randaccio, L.;
Pavone, V.; DeGrado, W. F. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6298-6305].
The overall structure of DF1, which contains a carboxylate-bridged dinuclear
metal site, agrees well with the intended design. However, access to this
dimetal site is blocked by a pair of hydrophobic leucine residues (L13 and
L13'), which prevent facile entry of metal ions and small molecules. We have now
taken the next step in the eventual construction of a catalytically active
metalloenzyme by engineering an active site cavity into DF1 through the
replacement of these two leucine residues with smaller residues. The crystal
structure of the dimanganous form of L13A-DF1 indeed shows a substrate access
channel to the dimetal center. In the crystal structure, water molecules and a
ligating dimethyl sulfoxide molecule, which forms a monatomic bridge between the
metal ions, occupy the cavity. Furthermore, the diferric form of a derivative of
L13A-DF1, DF2, is shown to bind azide, acetate, and small aromatic molecules.
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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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R.Torres Martin de Rosales,
M.Faiella,
E.Farquhar,
L.Que,
C.Andreozzi,
V.Pavone,
O.Maglio,
F.Nastri,
and
A.Lombardi
(2010).
Spectroscopic and metal-binding properties of DF3: an artificial protein able to accommodate different metal ions.
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J Biol Inorg Chem,
15,
717-728.
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C.B.Bell,
J.R.Calhoun,
E.Bobyr,
P.P.Wei,
B.Hedman,
K.O.Hodgson,
W.F.Degrado,
and
E.I.Solomon
(2009).
Spectroscopic definition of the biferrous and biferric sites in de novo designed four-helix bundle DFsc peptides: implications for O2 reactivity of binuclear non-heme iron enzymes.
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Biochemistry,
48,
59-73.
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J.R.Calhoun,
W.Liu,
K.Spiegel,
M.Dal Peraro,
M.L.Klein,
K.G.Valentine,
A.J.Wand,
and
W.F.DeGrado
(2008).
Solution NMR structure of a designed metalloprotein and complementary molecular dynamics refinement.
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Structure,
16,
210-215.
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PDB code:
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L.M.Jones,
W.Yang,
A.W.Maniccia,
A.Harrison,
P.A.van der Merwe,
and
J.J.Yang
(2008).
Rational design of a novel calcium-binding site adjacent to the ligand-binding site on CD2 increases its CD48 affinity.
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Protein Sci,
17,
439-449.
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R.Razeghifard
(2008).
Artificial photoactive proteins.
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Photosynth Res,
98,
677-685.
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H.Wade,
S.E.Stayrook,
and
W.F.Degrado
(2006).
The structure of a designed diiron(III) protein: implications for cofactor stabilization and catalysis.
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Angew Chem Int Ed Engl,
45,
4951-4954.
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K.Spiegel,
W.F.De Grado,
and
M.L.Klein
(2006).
Structural and dynamical properties of manganese catalase and the synthetic protein DF1 and their implication for reactivity from classical molecular dynamics calculations.
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Proteins,
65,
317-330.
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D.Noy,
B.M.Discher,
I.V.Rubtsov,
R.M.Hochstrasser,
and
P.L.Dutton
(2005).
Design of amphiphilic protein maquettes: enhancing maquette functionality through binding of extremely hydrophobic cofactors to lipophilic domains.
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Biochemistry,
44,
12344-12354.
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J.R.Calhoun,
F.Nastri,
O.Maglio,
V.Pavone,
A.Lombardi,
and
W.F.DeGrado
(2005).
Artificial diiron proteins: from structure to function.
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Biopolymers,
80,
264-278.
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O.Maglio,
F.Nastri,
J.R.Calhoun,
S.Lahr,
H.Wade,
V.Pavone,
W.F.DeGrado,
and
A.Lombardi
(2005).
Artificial di-iron proteins: solution characterization of four helix bundles containing two distinct types of inter-helical loops.
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J Biol Inorg Chem,
10,
539-549.
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J.Kaplan,
and
W.F.DeGrado
(2004).
De novo design of catalytic proteins.
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Proc Natl Acad Sci U S A,
101,
11566-11570.
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L.Di Costanzo,
F.Forneris,
S.Geremia,
and
L.Randaccio
(2003).
Phasing protein structures using the group-subgroup relation.
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Acta Crystallogr D Biol Crystallogr,
59,
1435-1439.
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PDB codes:
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O.Maglio,
F.Nastri,
V.Pavone,
A.Lombardi,
and
W.F.DeGrado
(2003).
Preorganization of molecular binding sites in designed diiron proteins.
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Proc Natl Acad Sci U S A,
100,
3772-3777.
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PDB code:
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P.D.Barker
(2003).
Designing redox metalloproteins from bottom-up and top-down perspectives.
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Curr Opin Struct Biol,
13,
490-499.
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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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