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PDBsum entry 6pyd
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Immune system
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PDB id
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6pyd
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References listed in PDB file
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Key reference
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Title
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Kappa-On-Heavy (koh) bodies are a distinct class of fully-Human antibody-Like therapeutic agents with antigen-Binding properties.
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Authors
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L.E.Macdonald,
K.A.Meagher,
M.C.Franklin,
N.Levenkova,
J.Hansen,
A.T.Badithe,
M.Zhong,
P.Krueger,
A.Rafique,
N.Tu,
J.Shevchuk,
S.Wadhwa,
G.Ehrlich,
J.Bautista,
C.Grant,
L.Esau,
W.T.Poueymirou,
W.Auerbach,
L.Morton,
R.Babb,
G.Chen,
T.Huang,
D.Macdonald,
K.Graham,
C.Gurer,
V.A.Voronina,
J.R.Mcwhirter,
C.Guo,
G.D.Yancopoulos,
A.J.Murphy.
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Ref.
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Proc Natl Acad Sci U S A, 2020,
117,
292-299.
[DOI no: ]
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PubMed id
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Abstract
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We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly
diverse, fully human, antibody-like agents. This mouse was made by replacing the
germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK)
loci with the human IgK germline variable sequences, producing antibody-like
molecules with an antigen binding site made up of 2 kappa variable domains.
These molecules, named KoH bodies, structurally mimic naturally existing
Bence-Jones light-chain dimers in their variable domains and remain wild-type in
their antibody constant domains. Unlike artificially diversified,
nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a
configuration of normal Ig scaffolds that undergo natural diversification in B
cells. Monoclonal KoH bodies have properties similar to those of conventional
antibodies but exhibit an enhanced ability to bind small molecules such as the
endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison
of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed
that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å
further down into the combining site between the 2 variable domains.
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Secondary reference #1
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Title
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Monoclonal antibody to an endogenous bufadienolide, Marinobufagenin, Reverses preeclampsia-Induced na/k-Atpase inhibition and lowers blood pressure in nacl-Sensitive hypertension.
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Authors
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O.V.Fedorova,
A.S.Simbirtsev,
N.I.Kolodkin,
A.Y.Kotov,
N.I.Agalakova,
V.A.Kashkin,
N.I.Tapilskaya,
A.Bzhelyansky,
V.A.Reznik,
E.V.Frolova,
E.R.Nikitina,
G.V.Budny,
D.L.Longo,
E.G.Lakatta,
A.Y.Bagrov.
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Ref.
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J Hypertens, 2008,
26,
2414-2425.
[DOI no: ]
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PubMed id
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