1JGV

STRUCTURAL BASIS FOR DISFAVORED ELIMINATION REACTION IN CATALYTIC ANTIBODY 1D4

Summary for 1JGV

• Entry DOI: 10.2210/pdb1jgv/pdb
• Related: 1JGU
• Descriptor: Antibody Light Chain, Antibody Heavy Chain (3 entities in total)
• Functional Keywords: igg fold, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 47857.55

Authors

Larsen, N.A.,Heine, A.,Crane, L.,Cravatt, B.F.,Lerner, R.A.,Wilson, I.A. (deposition date: 2001-06-26, release date: 2001-12-05, Last modification date: 2024-10-30)

Primary citation

Larsen, N.A.,Heine, A.,Crane, L.,Cravatt, B.F.,Lerner, R.A.,Wilson, I.A.
Structural basis for a disfavored elimination reaction in catalytic antibody 1D4.
J.Mol.Biol., 314:93-102, 2001

PubMed Abstract: 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.

PubMed: 11724535
DOI: 10.1006/jmbi.2001.5112

Experimental method

X-RAY DIFFRACTION (1.85 Å)