PDBsum entry 1mjj

Immune system

PDB id: 1mjj

Contents

Protein chains

218 a.a. *

211 a.a. *

Ligands

SO4 ×3

HAL ×2

Waters ×913

* Residue conservation analysis

PDB id:

1mjj

Name:

Immune system

Title:

High resolution crystal structure of the complex of the fab fragment of esterolytic antibody ms6-12 and a transition-state analog

Structure:

Immunoglobulin ms6-12. Chain: a, l. Fragment: fab fragment, light chain. Engineered: yes. Immunoglobulin ms6-12. Chain: b, h. Fragment: fab fragment, heavy chain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: hybridoma. Expressed in: mus musculus. Expression_system_taxid: 10090. Other_details: fusing of mouse splenocytes with myeloma cell. Other_details: fusing of mouse splenocytes with myeloma cell

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.178 R-free: 0.256

Authors:

S.N.Ruzheinikov,T.A.Muranova,S.E.Sedelnikova,L.J.Partridge, G.M.Blackburn,I.A.Murray,H.Kakinuma,N.Takashi,K.Shimazaki,J.Sun, Y.Nishi,D.W.Rice

Key ref:

S.N.Ruzheinikov et al. (2003). High-resolution crystal structure of the Fab-fragments of a family of mouse catalytic antibodies with esterase activity. J Mol Biol, 332, 423-435. PubMed id: 12948492 DOI: 10.1016/S0022-2836(03)00902-1

Date:

28-Aug-02 Release date: 23-Sep-03

Protein chains

No UniProt id for this chain

Struc: 218 a.a.

Protein chains

No UniProt id for this chain

Struc: 211 a.a.

DOI no: 10.1016/S0022-2836(03)00902-1

J Mol Biol 332:423-435 (2003)

PubMed id: 12948492

High-resolution crystal structure of the Fab-fragments of a family of mouse catalytic antibodies with esterase activity.

S.N.Ruzheinikov, T.A.Muranova, S.E.Sedelnikova, L.J.Partridge, G.M.Blackburn, I.A.Murray, H.Kakinuma, N.Takahashi-Ando, K.Shimazaki, J.Sun, Y.Nishi, D.W.Rice.

ABSTRACT

The crystal structures of four related Fab fragments of a family of catalytic antibodies displaying differential levels of esterase activity have been solved in the presence and in the absence of the transition-state analogue (TSA) that was used to elicit the immune response. The electron density maps show that the TSA conformation is essentially identical, with limited changes on hapten binding. Interactions with the TSA explain the specificity for the D rather than the L-isomer of the substrate. Differences in the residues in the hapten-binding pocket, which increase hydrophobicity, appear to correlate with an increase in the affinity of the antibodies for their substrate. Analysis of the structures at the active site reveals a network of conserved hydrogen bond contacts between the TSA and the antibodies, and points to a critical role of two conserved residues, HisL91 and LysH95, in catalysis. However, these two key residues are set into very different contexts in their respective structures, with an apparent direct correlation between the catalytic power of the antibodies and the complexity of their interactions with the rest of the protein. This suggests that the catalytic efficiency may be controlled by contacts arising from a second sphere of residues at the periphery of the active site.

Selected figure(s)

Figure 5.
Figure 5. A stereo picture of the superposition of a number of esterolytic abzymes with hapten bound in the active site. The superposition of the structures is based on the a-carbon coordinates corresponding to the variable part of the Fab structures. The protein chains are schematically shown only for the Fab12 structure. The colour scheme for carbon atoms of the different haptens is: grey, Fab12 (hapten: N-{[2-({[1-(4-carboxybutanoyl)amino]-2-phenylethyl}-hydroxyphosphinyl)oxy]acetyl}-2-phenylethyl-amine); green, 1A0Q (immunoglobulin 29G11,[27.] hapten: phenyl[1-(N-succinylamino) pentyl] phosphonate); red, 1AJ7 (immunoglobulin 48G7,[10.] hapten: 5-(para-nitrophenyl phosphonate)-pentanoic acid); blue, 1EAP (immunoglobulin 17E8,[4.] hapten: phenyl[1-(N-succinylamino) pentyl] phosphonate); yellow, 1KNO (immunoglobulin CNJ206,[5.] hapten: para-nitrophenyl-methyl-phosphorous acid); and light blue, 1YEI (immunoglobulin D2.3,[28.] hapten: para-nitrophenylphosphonobutanoyl-glycine).

Figure 7.
Figure 7. A stereo diagram showing the hydrogen bond network for the TSA bound in the Fab12/hapten structure, which is observed in all the Fab/hapten complexes. TyrL94, which is conserved in all the Fab structures studied here and which may play a role in protonation of the leaving group is also shown.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 332, 423-435) copyright 2003.

Figures were selected by an automated process.