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PDBsum entry 1cih
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Electron transport(heme protein)
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PDB id
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1cih
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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 functional effects of multiple mutations at distal sites in cytochrome c.
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Authors
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T.P.Lo,
S.Komar-Panicucci,
F.Sherman,
G.Mclendon,
G.D.Brayer.
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Ref.
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Biochemistry, 1995,
34,
5259-5268.
[DOI no: ]
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PubMed id
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Abstract
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Multiple mutations at distally located sites have been introduced into yeast
iso-1 cytochrome c to determine the contributions of three amino acids to the
structural and functional properties of this protein. The mutant proteins, for
which high-resolution structures were determined, included all possible
combinations of the substitutions Arg38Ala, Asn52Ile, and Phe82Ser. Arg38,
Asn52, and Phe82 are all conserved in the primary sequences of eukaryotic
cytochromes c and have been shown to significantly affect several properties of
these proteins including protein stability, heme reduction potential, and
oxidation state dependent conformational changes. The present studies show that
the structural consequences of each amino acid substitution in combinatorial
mutant proteins were similar to those observed in the related single-mutant
proteins, and therefore no synergistic effect between mutation sites was
observed for this feature. With respect to protein stability, the effect of
individual mutations can be understood from the structural changes observed for
each. It is found that stability effects of the three mutation sites are
independent and cumulative in multiple-mutant proteins. This reflects the
independent nature of the structural changes induced at the three distally
located mutation sites. In terms of heme reduction potential two effects are
observed. For substitution of Phe82 by serine, the mechanism by which reduction
potential is lowered is different from that occurring at either the Arg38 or the
Asn52 site and is independent of residue replacements at these latter two
positions. For Arg38 and Asn52, overlapping interactions lead to a higher
reduction potential than expected from a strict additive effect of substitutions
at these residues. This appears to arise from interaction of these two amino
acids with a common heme element, namely, the heme propionate A group. The
present results underscore the difficulty of predicting synergistic effects of
multiple mutations within a protein.
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Secondary reference #1
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Title
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The role of a conserved internal water molecule and its associated hydrogen bond network in cytochrome c.
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Authors
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A.M.Berghuis,
J.G.Guillemette,
G.Mclendon,
F.Sherman,
M.Smith,
G.D.Brayer.
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Ref.
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J Mol Biol, 1994,
236,
786-799.
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PubMed id
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Secondary reference #2
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Title
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Mutation of tyrosine-67 to phenylalanine in cytochrome c significantly alters the local heme environment.
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Authors
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A.M.Berghuis,
J.G.Guillemette,
M.Smith,
G.D.Brayer.
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Ref.
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J Mol Biol, 1994,
235,
1326-1341.
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PubMed id
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Secondary reference #3
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Title
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Oxidation state-Dependent conformational changes in cytochrome c.
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Authors
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A.M.Berghuis,
G.D.Brayer.
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Ref.
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J Mol Biol, 1992,
223,
959-976.
[DOI no: ]
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PubMed id
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Figure 3.
Figure 3. A schemtic representation of the atomic
skeleton of the heme group f cytochrome c and the atom
labeling convention used herein.
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Figure 10.
Figure 10. Drawings of the egion about the pyrrole
ing A propionate group in (a) reduced and (b) oxidized
yeast iso-l-cytochrome c, illustrating the positional shifts
nd altered hydrogen bonding patterns observed. The
yrrole ring A propionate group is hihlighted with dark
haded balls. Hydrogen bonds are indicated by hin
otted lines. The 2 internally bound water molecules,
Watl21 and -168, which mediate the interaction of Arg38
ith this heme propionate, are shown with largr spheres.
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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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High-Resolution refinement of yeast iso-1-Cytochrome c and comparisons with other eukaryotic cytochromes c.
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Authors
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G.V.Louie,
G.D.Brayer.
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Ref.
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J Mol Biol, 1990,
214,
527-555.
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PubMed id
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Secondary reference #5
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Title
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A polypeptide chain-Refolding event occurs in the gly82 variant of yeast iso-1-Cytochrome c.
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Authors
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G.V.Louie,
G.D.Brayer.
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Ref.
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J Mol Biol, 1989,
210,
313-322.
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PubMed id
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Secondary reference #6
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Title
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Crystallization of yeast iso-2-Cytochrome c using a novel hair seeding technique.
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Authors
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C.J.Leung,
B.T.Nall,
G.D.Brayer.
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Ref.
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J Mol Biol, 1989,
206,
783-785.
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PubMed id
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Secondary reference #7
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Title
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Role of phenylalanine-82 in yeast iso-1-Cytochrome c and remote conformational changes induced by a serine residue at this position.
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Authors
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G.V.Louie,
G.J.Pielak,
M.Smith,
G.D.Brayer.
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Ref.
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Biochemistry, 1988,
27,
7870-7876.
[DOI no: ]
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PubMed id
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Secondary reference #8
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Title
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Yeast iso-1-Cytochrome c. A 2.8 a resolution three-Dimensional structure determination.
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Authors
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G.V.Louie,
W.L.Hutcheon,
G.D.Brayer.
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Ref.
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J Mol Biol, 1988,
199,
295-314.
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PubMed id
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