1d5b: Difference between revisions
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'''UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY''' | {{Structure | ||
|PDB= 1d5b |SIZE=350|CAPTION= <scene name='initialview01'>1d5b</scene>, resolution 2.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CD:CADMIUM ION'>CD</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1D5B is a [ | 1D5B is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus_and_homo_sapiens Mus musculus and homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5B OCA]. | ||
==Reference== | ==Reference== | ||
Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement., Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC, Biochemistry. 2000 Feb 1;39(4):627-32. PMID:[http:// | Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement., Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC, Biochemistry. 2000 Feb 1;39(4):627-32. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10651626 10651626] | ||
[[Category: Mus musculus and homo sapiens]] | [[Category: Mus musculus and homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: immune system]] | [[Category: immune system]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:33:03 2008'' | ||
Revision as of 11:33, 20 March 2008
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY
OverviewOverview
Antibody AZ-28 was generated against the chairlike transition-state analogue (TSA) 1 and catalyzes the oxy-Cope rearrangement of substrate 2 to product 3. The germline precursor to AZ-28 catalyzes the reaction with a 35-fold higher rate (k(cat)/k(uncat) = 163 000), despite a 40-fold lower binding affinity for TSA.1 (K(D) = 670 nM). To determine the structural basis for the differences in the binding and catalytic properties of the germline and affinity-matured antibodies, the X-ray crystal structures of the unliganded and TSA.1 complex of antibody AZ-28 have been determined at 2.8 and 2.6 A resolution, respectively; the structures of the unliganded and TSA.1 complex of the germline precursor to AZ-28 were both determined at 2. 0 A resolution. In the affinity-matured antibody.hapten complex the TSA is fixed in a catalytically unfavorable conformation by a combination of van der Waals and hydrogen-bonding interactions. The 2- and 5-phenyl substituents of TSA.1 are almost perpendicular to the cyclohexyl ring, leading to decreased orbital overlap and decreased stabilization of the putative transition state. The active site of the germline antibody appears to have an increased degree of flexibility-CDRH3 moves 4.9 A outward from the active site upon binding of TSA.1. We suggest that this conformational flexibility in the germline antibody, which results in a lower binding affinity for TSA.1, allows dynamic changes in the dihedral angle of the 2-phenyl substituent along the reaction coordinate. These conformational changes in turn lead to enhanced orbital overlap and increased catalytic rate. These studies suggest that protein and substrate dynamics play a key role in this antibody-catalyzed reaction.
DiseaseDisease
Known disease associated with this structure: Kappa light chain deficiency OMIM:[147200]
About this StructureAbout this Structure
1D5B is a Protein complex structure of sequences from Mus musculus and homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement., Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC, Biochemistry. 2000 Feb 1;39(4):627-32. PMID:10651626
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