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1jgu
From Proteopedia
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STRUCTURAL BASIS FOR DISFAVORED ELIMINATION REACTION IN CATALYTIC ANTIBODY 1D4
Overview
Murine antibody 1D4 selectively catalyzes a highly disfavored, beta-elimination reaction. Crystal structures of unliganded 1D4 and 1D4 in, complex with a transition-state analog (TSA) have elucidated a possible, general base mode of catalysis. The structures of the unliganded and, liganded Fabs were determined to 1.80 and 1.85 A resolution, respectively., The structure of the complex reveals a binding pocket with high shape, complementarity to the TSA, which is recruited to coerce the substrate, into the sterically demanding, eclipsed conformation that is required for, catalysis. A histidine residue and two water molecules are likely involved, in the catalysis. The structure supports either a concerted E2 or stepwise, E1cB-like mechanism for elimination. Finally, the liganded 1D4 structure, shows minor conformational rearrangements in CDR H2, indicative of, induced-fit binding of the hapten. 1D4 has pushed the boundaries of, antibody-mediated catalysis into the realm of disfavored reactions and, hence, represents an important milestone in the development of this, technology.
About this Structure
1JGU is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for a disfavored elimination reaction in catalytic antibody 1D4., Larsen NA, Heine A, Crane L, Cravatt BF, Lerner RA, Wilson IA, J Mol Biol. 2001 Nov 16;314(1):93-102. PMID:11724535
Page seeded by OCA on Fri Feb 15 16:07:18 2008
Categories: Mus musculus | Single protein | Crane, L. | Cravatt, B.F. | Heine, A. | Larsen, N.A. | Lerner, R.A. | Wilson, I.A. | HBC | OH | Igg fold
