PDBsum entry 1y18

Immune system

PDB id: 1y18

Contents

Protein chains

216 a.a. *

226 a.a. *

Ligands

HAN ×4

Metals

_CL

Waters ×287

* Residue conservation analysis

PDB id:

1y18

Name:

Immune system

Title:

Fab fragment of catalytic elimination antibody 34e4 e(h50)d mutant in complex with hapten

Structure:

Catalytic antibody 34e4 light chain. Chain: l, a, c, e. Engineered: yes. Mutation: yes. Other_details: the variable domain (residues 1-107) is from a murine source and the constant domain (108-214) is from a human source. Catalytic antibody 34e4 heavy chain. Chain: h, b, d, f. Engineered: yes.

Source:

Mus musculus, homo sapiens. House mouse, human. Organism_taxid: 10090,9606. Strain: ,. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.80Å R-factor: 0.215 R-free: 0.252

Authors:

E.W.Debler,S.Ito,A.Heine,I.A.Wilson

Key ref:

E.W.Debler et al. (2005). Structural origins of efficient proton abstraction from carbon by a catalytic antibody. Proc Natl Acad Sci U S A, 102, 4984-4989. PubMed id: 15788533 DOI: 10.1073/pnas.0409207102

Date:

17-Nov-04 Release date: 05-Apr-05

Protein chains

No UniProt id for this chain

Struc: 216 a.a.

Protein chains

No UniProt id for this chain

Struc: 226 a.a.

DOI no: 10.1073/pnas.0409207102

Proc Natl Acad Sci U S A 102:4984-4989 (2005)

PubMed id: 15788533

Structural origins of efficient proton abstraction from carbon by a catalytic antibody.

E.W.Debler, S.Ito, F.P.Seebeck, A.Heine, D.Hilvert, I.A.Wilson.

ABSTRACT

Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-angstroms resolution shows that a combination of hydrogen bonding, pi stacking, and van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-angstroms structure of the Glu(H50)Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp(L91) and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acid-base pairs capable of bifunctional catalysis.

Selected figure(s)

Figure 2.
Fig. 2. Antibody-combining site of 34E4 bound to hapten. The heavy and light chains are colored in blue and green, respectively. Two of the active-site water molecules are designated S1 and S21. The 3F[o]-2F[c] [A]-weighted electron density map around the hapten and key active-site residues is contoured at 1.3 . Hydrogen bonds are shown as broken lines. TrpL91 forms a cation- interaction with the guanidinium moiety of the hapten. CDR H3 is omitted for clarity.

Figure 4.
Fig. 4. Stereoview of the antibody-combining site of the 34E4-hapten complex. Hydrogen bonds are shown as broken lines, and heavy and light chains are colored in blue and green, respectively. The hapten is sandwiched between two aromatic residues TrpL91 and TyrH100D. GluH50 forms a bidentate salt bridge to the guanidinium moiety of the hapten. The CDRs of the light and heavy chains are labeled L1-L3 and H1-H3, respectively.

Figures were selected by an automated process.