Anchoring a Cationic Ligand: The Structure of the Fab Fragment of the Anti-morphine Antibody 9B1 and its Complex with Morphine

Edwin Pozharski; Mark A. Wilson; Anura Hewagama; Armen B. Shanafelt; Gregory Petsko; Dagmar Ringe

doi:10.1016/j.jmb.2003.12.084

Anchoring a Cationic Ligand: The Structure of the Fab Fragment of the Anti-morphine Antibody 9B1 and its Complex with Morphine

Edwin Pozharski, Mark A. Wilson, Anura Hewagama, Armen B. Shanafelt, Gregory Petsko, Dagmar Ringe

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

The crystal structures of an anti-morphine antibody 9B1 (to 1.6Å resolution) and its complex with morphine (to 2.0Å resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity (K_a∼10⁹M^-1) antibody against a small antigen. The polar part of the ligand is exposed to solvent, and the cationic nitrogen atom of the morphine molecule is anchored at the bottom of the binding site by a salt-bridge to a glutamate side-chain. Additional affinity is provided by a double cation-π interaction with two tryptophan residues. Comparison of the morphine complex with the structure of the free Fab shows that a domain closure occurs upon binding of the ligand.

Original language	English (US)
Pages (from-to)	691-697
Number of pages	7
Journal	Journal of Molecular Biology
Volume	337
Issue number	3
DOIs	https://doi.org/10.1016/j.jmb.2003.12.084
State	Published - Mar 26 2004
Externally published	Yes

Keywords

CDR, complementarity determining region
Cation-π interaction
Domain motion
Electrostatics
Hapten
Protein-ligand interaction

ASJC Scopus subject areas

Molecular Biology
Biophysics
Structural Biology

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10.1016/j.jmb.2003.12.084

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title = "Anchoring a Cationic Ligand: The Structure of the Fab Fragment of the Anti-morphine Antibody 9B1 and its Complex with Morphine",

abstract = "The crystal structures of an anti-morphine antibody 9B1 (to 1.6{\AA} resolution) and its complex with morphine (to 2.0{\AA} resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity (Ka∼109M-1) antibody against a small antigen. The polar part of the ligand is exposed to solvent, and the cationic nitrogen atom of the morphine molecule is anchored at the bottom of the binding site by a salt-bridge to a glutamate side-chain. Additional affinity is provided by a double cation-π interaction with two tryptophan residues. Comparison of the morphine complex with the structure of the free Fab shows that a domain closure occurs upon binding of the ligand.",

keywords = "CDR, complementarity determining region, Cation-π interaction, Domain motion, Electrostatics, Hapten, Protein-ligand interaction",

author = "Edwin Pozharski and Wilson, {Mark A.} and Anura Hewagama and Shanafelt, {Armen B.} and Gregory Petsko and Dagmar Ringe",

note = "Funding Information: This work was supported by a grant from Roche Diagnostics, Inc. and by NIH grant GM26788 to G.A.P. and D.R.",

year = "2004",

month = mar,

day = "26",

doi = "10.1016/j.jmb.2003.12.084",

language = "English (US)",

volume = "337",

pages = "691--697",

journal = "Journal of Molecular Biology",

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T2 - The Structure of the Fab Fragment of the Anti-morphine Antibody 9B1 and its Complex with Morphine

AU - Pozharski, Edwin

AU - Wilson, Mark A.

AU - Hewagama, Anura

AU - Shanafelt, Armen B.

AU - Petsko, Gregory

AU - Ringe, Dagmar

N1 - Funding Information: This work was supported by a grant from Roche Diagnostics, Inc. and by NIH grant GM26788 to G.A.P. and D.R.

PY - 2004/3/26

Y1 - 2004/3/26

N2 - The crystal structures of an anti-morphine antibody 9B1 (to 1.6Å resolution) and its complex with morphine (to 2.0Å resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity (Ka∼109M-1) antibody against a small antigen. The polar part of the ligand is exposed to solvent, and the cationic nitrogen atom of the morphine molecule is anchored at the bottom of the binding site by a salt-bridge to a glutamate side-chain. Additional affinity is provided by a double cation-π interaction with two tryptophan residues. Comparison of the morphine complex with the structure of the free Fab shows that a domain closure occurs upon binding of the ligand.

AB - The crystal structures of an anti-morphine antibody 9B1 (to 1.6Å resolution) and its complex with morphine (to 2.0Å resolution) are reported. The morphine-binding site is described as a shallow depression on the protein surface, an unusual topology for a high-affinity (Ka∼109M-1) antibody against a small antigen. The polar part of the ligand is exposed to solvent, and the cationic nitrogen atom of the morphine molecule is anchored at the bottom of the binding site by a salt-bridge to a glutamate side-chain. Additional affinity is provided by a double cation-π interaction with two tryptophan residues. Comparison of the morphine complex with the structure of the free Fab shows that a domain closure occurs upon binding of the ligand.

KW - CDR, complementarity determining region

KW - Cation-π interaction

KW - Domain motion

KW - Electrostatics

KW - Hapten

KW - Protein-ligand interaction

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AN - SCOPUS:1542411577

SN - 0022-2836

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EP - 697

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 3

ER -

Anchoring a Cationic Ligand: The Structure of the Fab Fragment of the Anti-morphine Antibody 9B1 and its Complex with Morphine

Abstract

Keywords

ASJC Scopus subject areas

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