PDBsum entry 1c5b

Immune system

PDB id: 1c5b

Contents

Protein chains

214 a.a. *

215 a.a. *

Waters ×169

* Residue conservation analysis

PDB id:

1c5b

Name:

Immune system

Title:

Decarboxylase catalytic antibody 21d8 unliganded form

Structure:

Chimeric decarboxylase antibody 21d8. Chain: l. Fragment: fab. Engineered: yes. Other_details: the constant domain (residues 103-214) is from human source, and the variable domain (residues 1-102) is from murine source. Chimeric decarboxylase antibody 21d8. Chain: h.

Source:

Mus musculus, homo sapiens. House mouse, human. Organism_taxid: 10090,9606. Strain: balb/c, balb/c. Cell_line: 21d8. Organ: spleen. Cell: b-lymphocyte. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.188 R-free: 0.238

Authors:

K.Hotta,I.A.Wilson

Key ref:

K.Hotta et al. (2000). Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: crystal structures of abzyme 21D8. J Mol Biol, 302, 1213-1225. PubMed id: 11183784 DOI: 10.1006/jmbi.2000.4503

Date:

08-Nov-99 Release date: 11-Oct-00

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 215 a.a.

DOI no: 10.1006/jmbi.2000.4503

J Mol Biol 302:1213-1225 (2000)

PubMed id: 11183784

Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: crystal structures of abzyme 21D8.

K.Hotta, H.Lange, D.J.Tantillo, K.N.Houk, D.Hilvert, I.A.Wilson.

ABSTRACT

Antibody 21D8 catalyzes the solvent-sensitive decarboxylation of 3-carboxybenzisoxazoles. The crystal structure of chimeric Fab 21D8 with and without hapten at 1.61 A and 2.10 A, respectively, together with computational analysis, shows how a melange of polar and non-polar sites are exploited to achieve both substrate binding and acceleration of a reaction normally facilitated by purely aprotic dipolar media. The striking similarity of the decarboxylase and a series of unrelated esterase antibodies also highlights the chemical versatility of structurally conserved anion binding sites and the relatively subtle changes involved in fine-tuning the immunoglobulin pocket for recognition of different ligands and catalysis of different reactions.

Selected figure(s)

Figure 1.
Figure 1. Decarboxylation of 5-nitro-3-carboxybenzisoxazole 2 proceeds through a charge-delocalized transition state 3 to give salicylonitrile 4. Naphthalene disulfonate 1 was used to elicit the decarboxylase antibody 21D8 through a covalent linkage to keyhole limpet hemocyanin (KLH).

Figure 3.
Figure 3. The Fab 21D8 combining site with bound hapten. (a) Molecular surface representation of the 21D8 binding pocket region. Hapten sulfonate groups bind in regions that are positively charged (blue), while the naphthalene moiety is entirely buried within an apolar pocket (gray). (b) View of the 21D8 hapten binding site showing all the hapten-contacting residues and their molecular interactions with the hapten. The coloring scheme is the same as for Figure 2. (c) View of the hapten binding pocket of the unliganded 21D8 structure, showing the side-chain conformations of the hapten-contacting residues and the bound water molecules (red spheres). The hapten complex structure (darker color for Fab) is overlaid to emphasize the position of the bound hapten (semitransparent structure) and the slight differences in the binding site conformations.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2000, 302, 1213-1225) copyright 2000.

Figures were selected by an automated process.