2bjm
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Induced fit is a predominant phenomenon in protein-ligand interactions, yet it is invariably attributed without establishing the existence, let | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Rattus rattus]] | [[Category: Rattus rattus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: James, L | + | [[Category: James, L C.]] |
| - | [[Category: Tawfik, D | + | [[Category: Tawfik, D S.]] |
[[Category: ANF]] | [[Category: ANF]] | ||
[[Category: antibody]] | [[Category: antibody]] | ||
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[[Category: promiscuity]] | [[Category: promiscuity]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:38:32 2008'' |
Revision as of 14:38, 21 February 2008
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SPE7:ANTHRONE COMPLEX
Overview
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.
About this Structure
2BJM is a Single protein structure of sequence from Rattus rattus with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structure and kinetics of a transient antibody binding intermediate reveal a kinetic discrimination mechanism in antigen recognition., James LC, Tawfik DS, Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12730-5. Epub 2005 Aug 29. PMID:16129832
Page seeded by OCA on Thu Feb 21 16:38:32 2008
