PDBsum entry 1kno

Catalytic antibody

PDB id

1kno

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Contents

			Protein chains

					214 a.a. *


					220 a.a. *

			Ligands

					PNP ×3

			Metals

					_ZN

* Residue conservation analysis

PDB id:

1kno

Links

Name:

Catalytic antibody

Title:

Crystal structure of the complex of a catalytic antibody fab with a transition state analog: structural similarities in esterase-like abzymes

Structure:

Igg2a fab fragment cnj206. Chain: a, c, e. Igg2a fab fragment cnj206. Chain: b, d, f

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Strain: balb/c

Biol. unit:

Dimer (from PQS)

Resolution:

3.20Å

R-factor:

0.200

R-free:

0.272

Authors:

J.-B.Charbonnier,B.Gigant,M.Knossow

Key ref:

J.B.Charbonnier et al. (1995). Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies. Proc Natl Acad Sci U S A, 92, 11721-11725. PubMed id: 8524836 DOI: 10.1073/pnas.92.25.11721

Date:

11-Sep-95

Release date:

29-Jan-96

PROCHECK

	Headers

	References

Protein chains

P01837 (IGKC_MOUSE) - Immunoglobulin kappa constant from Mus musculus

Seq: Struc:					107 a.a. 214 a.a.

Protein chains

P01863 (GCAA_MOUSE) - Ig gamma-2A chain C region, A allele from Mus musculus

Seq: Struc:					330 a.a. 220 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

DOI no: 10.1073/pnas.92.25.11721	Proc Natl Acad Sci U S A 92:11721-11725 (1995)
PubMed id: 8524836

Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies.
J.B.Charbonnier, E.Carpenter, B.Gigant, B.Golinelli-Pimpaneau, Z.Eshhar, B.S.Green, M.Knossow.

ABSTRACT

The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests hapten-induced conformational changes: the shape of the combining site changes from a shallow groove in the uncomplexed Fab to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to stabilize the charged phosphonate group of the hapten: two NH groups of the heavy (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining site shows striking structural similarities to that of antibody 17E8, which also has esterase activity. Both catalytic antibody ("abzyme") structures suggest that oxyanion stabilization plays a significant role in their rate acceleration. Additional catalytic groups that improve efficiency are not necessarily induced by the eliciting hapten; these groups may occur because of the variability in the combining sites of different monoclonal antibodies that bind to the same hapten.

Literature references that cite this PDB file's key reference

PubMed id

Reference

19776018

I.C.Wilkinson, C.J.Hall, V.Veverka, J.Y.Shi, F.W.Muskett, P.E.Stephens, R.J.Taylor, A.J.Henry, and M.D.Carr (2009).
High resolution NMR-based model for the structure of a scFv-IL-1beta complex: potential for NMR as a key tool in therapeutic antibody design and development.

J Biol Chem, 284, 31928-31935.

PDB code:

2kh2

18417480

E.W.Debler, R.Müller, D.Hilvert, and I.A.Wilson (2008).
Conformational isomerism can limit antibody catalysis.

J Biol Chem, 283, 16554-16560.

PDB codes:

3cfj 3cfk

17400249

E.W.Debler, G.F.Kaufmann, R.N.Kirchdoerfer, J.M.Mee, K.D.Janda, and I.A.Wilson (2007).
Crystal structures of a quorum-quenching antibody.

J Mol Biol, 368, 1392-1402.

PDB codes:

2ntf 2op4

17116886

J.Racape, F.Connan, J.Hoebeke, J.Choppin, and J.G.Guillet (2006).
Influence of dominant HIV-1 epitopes on HLA-A3/peptide complex formation.

Proc Natl Acad Sci U S A, 103, 18208-18213.

15880452

J.L.Pellequer, S.W.Chen, Y.S.Keum, A.E.Karu, Q.X.Li, and V.A.Roberts (2005).
Structural basis for preferential binding of non-ortho-substituted polychlorinated biphenyls by the monoclonal antibody S2B1.

J Mol Recognit, 18, 282-294.

11468416

T.A.Muranova, S.N.Ruzheinikov, S.E.Sedelnikova, A.Moir, L.J.Partridge, H.Kakinuma, N.Takahashi, K.Shimazaki, J.Sun, Y.Nishi, and D.W.Rice (2001).
The preparation and crystallization of Fab fragments of a family of mouse esterolytic catalytic antibodies and their complexes with a transition-state analogue.

Acta Crystallogr D Biol Crystallogr, 57, 1192-1195.

11575776

T.Tsumuraya, N.Takazawa, A.Tsunakawa, R.Fleck, and S.Masamune (2001).
Catalytic antibodies induced by a zwitterionic hapten.

Chemistry, 7, 3748-3755.

11095704

A.V.Kolesnikov, A.V.Kozyr, E.S.Alexandrova, F.Koralewski, A.V.Demin, M.I.Titov, B.Avalle, A.Tramontano, S.Paul, D.Thomas, A.G.Gabibov, and A.Friboulet (2000).
Enzyme mimicry by the antiidiotypic antibody approach.

Proc Natl Acad Sci U S A, 97, 13526-13531.

10963661

B.Golinelli-Pimpaneau, O.Goncalves, T.Dintinger, D.Blanchard, M.Knossow, and C.Tellier (2000).
Structural evidence for a programmed general base in the active site of a catalytic antibody.

Proc Natl Acad Sci U S A, 97, 9892-9895.

PDB code:

1f3d

11114507

B.Golinelli-Pimpaneau (2000).
Novel reactions catalysed by antibodies.

Curr Opin Struct Biol, 10, 697-708.

10966475

D.Hilvert (2000).
Critical analysis of antibody catalysis.

Annu Rev Biochem, 69, 751-793.

10214693

B.Avalle, V.Zanin, D.Thomas, and A.Friboulet (1998).
Antibody catalysis based on functional mimicry.

Appl Biochem Biotechnol, 75, 3.

9359117

A.Persidis (1997).
Catalytic antibodies. Some companies are taking an active interest in this promising technology.

Nat Biotechnol, 15, 1313-1315.

9208940

B.Gigant, J.B.Charbonnier, B.Golinelli-Pimpaneau, R.R.Zemel, Z.Eshhar, B.S.Green, and M.Knossow (1997).
Mechanism of inactivation of a catalytic antibody by p-nitrophenyl esters.

Eur J Biochem, 246, 471-476.

9223277

B.Gigant, J.B.Charbonnier, Z.Eshhar, B.S.Green, and M.Knossow (1997).
X-ray structures of a hydrolytic antibody and of complexes elucidate catalytic pathway from substrate binding and transition state stabilization through water attack and product release.

Proc Natl Acad Sci U S A, 94, 7857-7861.

PDB codes:

1yef 1yeg 1yeh

9241427

H.Wade, and T.S.Scanlan (1997).
The structural and functional basis of antibody catalysis.

Annu Rev Biophys Biomol Struct, 26, 461-493.

9027317

J.B.Charbonnier, B.Golinelli-Pimpaneau, B.Gigant, D.S.Tawfik, R.Chap, D.G.Schindler, S.H.Kim, B.S.Green, Z.Eshhar, and M.Knossow (1997).
Structural convergence in the active sites of a family of catalytic antibodies.

Science, 275, 1140-1142.

PDB codes:

1yec 1yed 1yee

8643580

L.C.Hsieh-Wilson, P.G.Schultz, and R.C.Stevens (1996).
Insights into antibody catalysis: structure of an oxygenation catalyst at 1.9-angstrom resolution.

Proc Natl Acad Sci U S A, 93, 5363-5367.

PDB codes:

1kel 1kem

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.