PDBsum entry 1jpt

Immune system

PDB id

1jpt

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Contents

			Protein chains

					213 a.a. *


					212 a.a. *

			Waters ×372

* Residue conservation analysis

PDB id:

1jpt

Links

Name:

Immune system

Title:

Crystal structure of fab d3h44

Structure:

Immunoglobulin fab d3h44, light chain. Chain: l. Fragment: fab fragment. Engineered: yes. Immunoglobulin fab d3h44, heavy chain. Chain: h. Fragment: fab fragment. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.85Å

R-factor:

0.182

R-free:

0.228

Authors:

K.Faelber,D.Kirchhofer,L.Presta,R.F.Kelley,Y.A.Muller

Key ref:

K.Faelber et al. (2001). The 1.85 A resolution crystal structures of tissue factor in complex with humanized Fab D3h44 and of free humanized Fab D3h44: revisiting the solvation of antigen combining sites. J Mol Biol, 313, 83-97. PubMed id: 11601848 DOI: 10.1006/jmbi.2001.5036

Date:

03-Aug-01

Release date:

03-Feb-02

PROCHECK

	Headers

	References

Protein chain

No UniProt id for this chain

Struc:					213 a.a.

Protein chain

No UniProt id for this chain

Struc:					212 a.a.

Key:

Secondary structure

CATH domain

DOI no: 10.1006/jmbi.2001.5036	J Mol Biol 313:83-97 (2001)
PubMed id: 11601848

The 1.85 A resolution crystal structures of tissue factor in complex with humanized Fab D3h44 and of free humanized Fab D3h44: revisiting the solvation of antigen combining sites.
K.Faelber, D.Kirchhofer, L.Presta, R.F.Kelley, Y.A.Muller.

ABSTRACT

The outstanding importance of the antigen-antibody recognition process for the survival and defence strategy of higher organisms is in sharp contrast to the limited high resolution structural data available on antibody-antigen pairs with antigenic proteins. The limitation is the most severe for structural data not restricted to the antigen-antibody complex but extending to the uncomplexed antigen and antibody. We report the crystal structure of the complex between tissue factor (TF) and the humanized Fab fragment D3h44 at a resolution of 1.85 A together with the structure of uncomplexed D3h44 at the same resolution. In conjunction with the previously reported 1.7 A crystal structure of uncomplexed TF, a unique opportunity is generated to explore details of the recognition process. The TF.D3h44 interface is characterised by a high number of polar interactions, including as may as 46 solvent molecules. Conformational changes upon complex formation are very small and almost exclusively limited to the reorientation of side-chains. The binding epitope is in complete agreement with earlier mutagenesis experiments. A revaluation of two other antibody-antigen pairs reported at similar resolutions, shows that all these complexes are very similar with respect to the solvation of the interface, the number of solvent positions conserved in the uncomplexed and complexed proteins and the number of water molecules expelled from the surface and replaced by hydrophilic atoms from the binding partner upon complex formation. A strategy is proposed on how to exploit this high resolution structural data to guide the affinity maturation of humanised antibodies.

Selected figure(s)



	Figure 1. Figure 1. Ribbon representation of TF (in red) in complex with D3h44 (light chain in light blue and heavy chain in dark blue). D3h44 recognizes a binding epitope located in the C-terminal FNIII domain of the ectodomain of TF. The b-strands of the C-terminal FNIII domain of TF are labeled as established for the topologically similar C2-type immunoglobulins.[34 and 35] This figure and all following model illustrations have been prepared with program MOLMOL. [61]		Figure 5. Figure 5. Stereo representation of the highly complementary hydrophilic interaction patch centered on Asp-H52. The TF backbone is shown in red and the backbone of the CDRs from the heavy chain in dark blue.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20062929

J.A.Jiao, A.B.Kelly, U.M.Marzec, E.Nieves, J.Acevedo, M.Burkhardt, A.Edwards, X.Y.Zhu, P.A.Chavaillaz, A.Wong, J.L.Wong, J.O.Egan, D.Taylor, P.R.Rhode, and H.C.Wong (2010).
Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site.

Thromb Haemost, 103, 224-233.

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

17001032

P.Haste Andersen, M.Nielsen, and O.Lund (2006).
Prediction of residues in discontinuous B-cell epitopes using protein 3D structures.

Protein Sci, 15, 2558-2567.

16553557

S.G.Park, Y.J.Jung, Y.Y.Lee, C.M.Yang, I.J.Kim, J.H.Chung, I.S.Kim, Y.J.Lee, S.J.Park, J.N.Lee, S.K.Seo, Y.H.Park, and I.H.Choi (2006).
Improvement of neutralizing activity of human scFv antibodies against hepatitis B virus binding using CDR3 V(H) mutant library.

Viral Immunol, 19, 115-123.

15564505

W.D.Crill, and G.J.Chang (2004).
Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes.

J Virol, 78, 13975-13986.

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.