1KNO

CRYSTAL STRUCTURE OF THE COMPLEX OF A CATALYTIC ANTIBODY FAB WITH A TRANSITION STATE ANALOG: STRUCTURAL SIMILARITIES IN ESTERASE-LIKE ABZYMES

Summary for 1KNO

• Entry DOI: 10.2210/pdb1kno/pdb
• Descriptor: IGG2A FAB FRAGMENT CNJ206, ZINC ION, METHYL-PHOSPHONIC ACID MONO-(4-NITRO-PHENYL) ESTER, ... (4 entities in total)
• Functional Keywords: catalytic antibody
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 6
• Total formula weight: 141720.32

Authors

Charbonnier, J.-B.,Gigant, B.,Knossow, M. (deposition date: 1995-09-11, release date: 1996-01-29, Last modification date: 2024-10-30)

Primary citation

Charbonnier, J.B.,Carpenter, E.,Gigant, B.,Golinelli-Pimpaneau, B.,Eshhar, Z.,Green, B.S.,Knossow, M.
Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies.
Proc.Natl.Acad.Sci.USA, 92:11721-11725, 1995

PubMed Abstract: The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests hapten-induced conformational changes: the shape of the combining site changes from a shallow groove in the uncomplexed Fab to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to stabilize the charged phosphonate group of the hapten: two NH groups of the heavy (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining site shows striking structural similarities to that of antibody 17E8, which also has esterase activity. Both catalytic antibody ("abzyme") structures suggest that oxyanion stabilization plays a significant role in their rate acceleration. Additional catalytic groups that improve efficiency are not necessarily induced by the eliciting hapten; these groups may occur because of the variability in the combining sites of different monoclonal antibodies that bind to the same hapten.

PubMed: 8524836
DOI: 10.1073/pnas.92.25.11721

Experimental method

X-RAY DIFFRACTION (3.2 Å)