2BJM

SPE7:Anthrone Complex

Summary for 2BJM

• Entry DOI: 10.2210/pdb2bjm/pdb
• Descriptor: IGE SPE7 HEAVY CHAIN, IGE SPE7 LIGHT CHAIN, ANTHRONE (3 entities in total)
• Functional Keywords: immune system, encounter complex
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Total number of polymer chains: 2
• Total formula weight: 25298.21

Authors

James, L.C.,Tawfik, D.S. (deposition date: 2005-02-04, release date: 2005-08-18, Last modification date: 2024-11-06)

Primary citation

James, L.C.,Tawfik, D.S.
Structure and Kinetics of a Transient Antibody Binding Intermediate Reveal a Kinetic Discrimination Mechanism in Antigen Recognition
Proc.Natl.Acad.Sci.USA, 102:12730-, 2005

PubMed Abstract: Induced fit is a predominant phenomenon in protein-ligand interactions, yet it is invariably attributed without establishing the existence, let alone the structure, of the initial, low-affinity encounter complex. We determined the crystal structure of the encounter complex on the pathway of ligand binding by IgE antibody SPE7. We show that this complex is formed by a wide range of ligands that initially bind with identical affinity. Nonspecific ligands rapidly dissociate, whereupon the antibody isomerizes to a nonbinding isomer. Specific ligand complexes, however, slowly isomerize to give a high-affinity complex. This isomerization involves backbone and side-chain rearrangements of up to 14 A and the formation of specific hydrogen bonds. The postbinding conformational switch, combined with the prebinding isomerization to an energetically favorable nonbinding isomer, results in a "kinetic discrimination" mechanism that mediates selective binding, by a factor of >10(3), between highly related ligands that initially bind with the same affinity. This model may apply to proteins that bind multiple ligands in a specific manner or other proteins that, although capable of binding many ligands, are activated by only a few.

PubMed: 16129832
DOI: 10.1073/PNAS.0500909102

Experimental method

X-RAY DIFFRACTION (2.15 Å)