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PDBsum entry 1mcs
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Immunoglobulin
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PDB id
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1mcs
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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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Principles and pitfalls in designing site-Directed peptide ligands.
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Authors
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A.B.Edmundson,
D.L.Harris,
Z.C.Fan,
L.W.Guddat,
B.T.Schley,
B.L.Hanson,
G.Tribbick,
H.M.Geysen.
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Ref.
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Proteins, 1993,
16,
246-267.
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PubMed id
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Abstract
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An immunoglobulin light chain dimer with a large generic binding cavity was used
as a host molecule for designing a series of peptide guest ligands. In a
screening procedure peptides coupled to solid supports were systematically
tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key
members of the binding series were synthesized in milligram quantities and
diffused into crystals of the host molecule for X-ray analyses. These peptides
were incrementally increased in size and affinity until they nearly filled the
cavity. Progressive changes in binding patterns were mapped by comparisons of
crystallographically refined structures of 14 peptide-protein complexes at 2.7 A
resolution. These comparisons led to guidelines for ligand design and also
suggested ways to modify previously established binding patterns. By
manipulating equilibria involving histidine, for example, it was possible to
abolish one important intramolecular interaction of the bound ligand and
substitute another. These events triggered a change in conformation of the
ligand from a compact to an extended form and a comprehensive change in the mode
of binding to the protein. In dipeptides of histidine and proline, protonation
of both imidazolium nitrogen atoms was used to program an end-to-end reversal of
the direction in which the ligand was inserted into the binding cavity. Peptides
cocrystallized with proteins produced complexes somewhat different in structure
from those in which ligands were diffused into preexisting crystals. In such a
large and malleable cavity, space utilization was thus different when a ligand
was introduced before the imposition of crystal packing restraints.
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Secondary reference #1
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Title
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The binding of opioid peptides to the mcg light chain dimer: flexible keys and adjustable locks.
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Authors
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A.B.Edmundson,
K.R.Ely,
J.N.Herron,
B.D.Cheson.
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Ref.
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Mol Immunol, 1987,
24,
915-935.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Binding of n-Formylated chemotactic peptides in crystals of the mcg light chain dimer: similarities with neutrophil receptors.
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Authors
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A.B.Edmundson,
K.R.Ely.
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Ref.
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Mol Immunol, 1985,
22,
463-475.
[DOI no: ]
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PubMed id
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Secondary reference #3
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Title
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A search for site-Filling ligands in the mcg bence-Jones dimer: crystal binding studies of fluorescent compounds.
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Authors
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A.B.Edmundson,
K.R.Ely,
J.N.Herron.
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Ref.
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Mol Immunol, 1984,
21,
561-576.
[DOI no: ]
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PubMed id
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Secondary reference #4
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Title
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Binding of 2,4-Dinitrophenyl compounds and other small molecules to a crystalline lambda-Type bence-Jones dimer.
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Authors
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A.B.Edmundson,
K.R.Ely,
R.L.Girling,
E.E.Abola,
M.Schiffer,
F.A.Westholm,
M.D.Fausch,
H.F.Deutsch.
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Ref.
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Biochemistry, 1974,
13,
3816-3827.
[DOI no: ]
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PubMed id
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