PDBsum entry 1ct8

Immune system

PDB id: 1ct8

Contents

Protein chains

214 a.a.

220 a.a. *

Ligands

SO4 ×2

TAA ×2

Waters ×195

* Residue conservation analysis

PDB id:

1ct8

Name:

Immune system

Title:

Catalytic antibody 7c8 complex

Structure:

7c8 fab fragment. Short chain. Chain: a, c. 7c8 fab fragment. Long chain. Chain: b, d

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å R-factor: 0.211 R-free: 0.275

Authors:

B.Gigant,T.Tsumuraya,I.Fujii,M.Knossow

Key ref:

B.Gigant et al. (1999). Diverse structural solutions to catalysis in a family of antibodies. Structure, 7, 1385-1393. PubMed id: 10574796 DOI: 10.1016/S0969-2126(00)80028-3

Date:

20-Aug-99 Release date: 10-Nov-99

Protein chains

P01837  (IGKC_MOUSE) -  Immunoglobulin kappa constant from Mus musculus

Seq: 107 a.a.

Struc: 214 a.a.

Protein chains

P01868  (IGHG1_MOUSE) -  Ig gamma-1 chain C region secreted form from Mus musculus

Seq: 324 a.a.

Struc: 220 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/S0969-2126(00)80028-3

Structure 7:1385-1393 (1999)

PubMed id: 10574796

Diverse structural solutions to catalysis in a family of antibodies.

B.Gigant, T.Tsumuraya, I.Fujii, M.Knossow.

ABSTRACT

BACKGROUND: Small organic molecules coupled to a carrier protein elicit an antibody response on immunisation. The diversity of this response has been found to be very narrow in several cases. Some antibodies also catalyse chemical reactions. Such catalytic antibodies are usually identified among those that bind tightly to an analogue of the transition state (TSA) of the relevant reaction; therefore, catalytic antibodies are also thought to have restricted diversity. To further characterise this diversity, we investigated the structure and biochemistry of the catalytic antibody 7C8, one of the most efficient of those which enhance the hydrolysis of chloramphenicol esters, and compared it to the other catalytic antibodies elicited in the same immunisation. RESULTS: The structure of a complex of the 7C8 antibody Fab fragment with the hapten TSA used to elicit it was determined at 2.2 A resolution. Structural comparison with another catalytic antibody (6D9) raised against the same hapten revealed that the two antibodies use different binding modes. Furthermore, whereas 6D9 catalyses hydrolysis solely by transition-state stabilisation, data on 7C8 show that the two antibodies use mechanisms where the catalytic residue, substrate specificity and rate-limiting step differ. CONCLUSIONS: Our results demonstrate that substantial diversity may be present among antibodies catalysing the same reaction. Therefore, some of these antibodies represent different starting points for mutagenesis aimed at boosting their activity. This increases the chance of obtaining more proficient catalysts and provides opportunities for tailoring catalysts with different specificities.

Selected figure(s)

Figure 1.
Figure 1. Chemical formulae of the compounds used in this study. Antibody 7C8 was raised against the chloramphenicol phosphonate 1 and catalyses the hydrolysis of the chloramphenicol ester 2 to generate the acid product and chloramphenicol 3. TSA 4 was used to elicit the p-nitrobenzyl ester hydrolysing antibody D2.3 [49].

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1385-1393) copyright 1999.

Figure was selected by an automated process.