PDBsum entry 1a0q

Catalytic antibody

PDB id: 1a0q

Contents

Protein chains

211 a.a. *

205 a.a. *

Ligands

HEP

Metals

_ZN ×3

Waters ×92

* Residue conservation analysis

References listed in PDB file

Key reference

Title

A comparison of the crystallographic structures of two catalytic antibodies with esterase activity.

Authors

J.L.Buchbinder, R.C.Stephenson, T.S.Scanlan, R.J.Fletterick.

Ref.

J Mol Biol, 1998, 282, 1033-1041. [DOI no: 10.1006/jmbi.1998.2025]

PubMed id

9753552

Abstract

The crystallographic structure of the Fab fragment of the catalytic antibody, 29G11, complexed with an (S)-norleucine phenyl phosphonate transition state analog was determined at 2.2 A resolution. The antibody catalyzes the hydrolysis of norleucine phenyl ester with (S)-enantioselectivity. The shape and charge complementarity of the binding pocket for the hapten account for the preferential binding of the (S)-enantiomer of the substrate. The structure is compared to that of the more catalytically efficient antibody, 17E8, induced by the same hapten transition state analog. 29G11 has different residues from 17E8 at eight positions in the heavy chain, including four substitutions in the hapten-binding pocket: A33V, S95G, S99R and Y100AN, and four substitutions at positions remote from the catalytic site, I28T, R40K, V65G and F91L. The two antibodies show large differences in the orientations of their variable and constant domains, reflected by a 32 degrees difference in their elbow angles. The VL and VH domains in the two antibodies differ by a rotation of 8.8 degrees. The hapten binds in similar orientations and locations in 29G11 and 17E8, which appear to have catalytic groups in common, though the changes in the association of the variable domains affect the precise positioning of residues in the hapten-binding pocket.

Figure 2.
Figure 2. Stereo view of the 2Fo - Fc electron density map contoured at 1.0 s shows the region in the vicinity of the hapten at the catalytic site of 29G11. The hapten is colored yellow. This Figure was prepared with the program O (Jones et al., 1991).

Figure 4.
Figure 4. View of hapten-binding site. Residues within 4.2 Å of the hapten are shown. Arg L96 forms hydrogen bonds with the amide carbonyl oxygen atom, the pro-R phosphonate oxygen atom, and the bridging phosphonate oxygen atom of the hapten. Charged hydrogen bonds are formed between the NH3 group of Lys H93 and the pro-S phosphonate oxygen atom of the hapten. The norleucine side-chain of the hapten is sur- rounded by the hydrophobic residues: Tyr L36, Leu L46, Leu L89 and Tyr L91. Recognition of the phenyl ring of the hapten is mediated by the aromatic residues Phe L98, Tyr L36, Trp H47 and Trp H103.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 282, 1033-1041) copyright 1998.

Secondary reference #1

Title

Crystal structure of a catalytic antibody with a serine protease active site.

Authors

G.W.Zhou, J.Guo, W.Huang, R.J.Fletterick, T.S.Scanlan.

Ref.

Science, 1994, 265, 1059-1064. [DOI no: 10.1126/science.8066444]

PubMed id

8066444