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PDBsum entry 1fgv

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protein Protein-protein interface(s) links
Immune system PDB id
1fgv
Jmol
Contents
Protein chains
107 a.a. *
120 a.a. *
Waters ×109
* Residue conservation analysis
PDB id:
1fgv
Name: Immune system
Title: X-ray structures of fragments from binding and nonbinding ve a humanized anti-cd18 antibody: structural indications of t role of vh residues 59 to 65
Structure: H52 fv (light chain). Chain: l. Engineered: yes. H52 fv (heavy chain). Chain: h. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.180    
Authors: C.Eigenbrot,J.Kessler
Key ref: C.Eigenbrot et al. (1994). X-ray structures of fragments from binding and nonbinding versions of a humanized anti-CD18 antibody: structural indications of the key role of VH residues 59 to 65. Proteins, 18, 49-62. PubMed id: 7908437
Date:
01-Nov-93     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 107 a.a.
Protein chain
No UniProt id for this chain
Struc: 120 a.a.
Key:    Secondary structure  CATH domain

 

 
Proteins 18:49-62 (1994)
PubMed id: 7908437  
 
 
X-ray structures of fragments from binding and nonbinding versions of a humanized anti-CD18 antibody: structural indications of the key role of VH residues 59 to 65.
C.Eigenbrot, T.Gonzalez, J.Mayeda, P.Carter, W.Werther, T.Hotaling, J.Fox, J.Kessler.
 
  ABSTRACT  
 
X-ray crystal structures of fragments from two different humanized anti-CD18 antibodies are reported. The Fv fragment of the nonbinding version has been refined in space group C2 with a = 64.2 A, b = 61.3 A, c = 51.8 A, and beta = 99 degrees to an R-value of 18.0% at 1.9 A, and the Fab fragment of the tight-binding version has been refined in space group P3 with a = 101. A and c = 45.5 A to an R-value of 17.8% at 3.0 A resolution. The very large difference in their binding affinity (> 1000-fold) is attributed to large and local structural differences in the C-terminal part of CDR-H2, and from this we conclude there is direct contact between this region and antigen when they combine. X-ray structures of antibody-antigen complexes available in the literature have yet to show this part of CDR-H2 in contact with antigen, despite its hypervariable sequence. Implications of this result for antibody humanization are discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19022801 M.Schlapschy, M.Fogarasi, H.Gruber, O.Gresch, C.Schäfer, Y.Aguib, and A.Skerra (2009).
Functional humanization of an anti-CD16 Fab fragment: obstacles of switching from murine {lambda} to human {lambda} or {kappa} light chains.
  Protein Eng Des Sel, 22, 175-188.  
16151804 C.W.Adams, D.E.Allison, K.Flagella, L.Presta, J.Clarke, N.Dybdal, K.McKeever, and M.X.Sliwkowski (2006).
Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab.
  Cancer Immunol Immunother, 55, 717-727.  
16782791 P.J.Kundrotas, and E.Alexov (2006).
Electrostatic properties of protein-protein complexes.
  Biophys J, 91, 1724-1736.  
16189008 R.A.Wilkinson, C.Piscitelli, M.Teintze, L.A.Cavacini, M.R.Posner, and C.M.Lawrence (2005).
Structure of the Fab fragment of F105, a broadly reactive anti-human immunodeficiency virus (HIV) antibody that recognizes the CD4 binding site of HIV type 1 gp120.
  J Virol, 79, 13060-13069.
PDB code: 1u6a
15319072 M.Huang, B.Zhang, J.Wang, F.Mei, and L.Hou (2004).
Development of single-domain recombinant antibodies to reverse transcriptase domain of human hTERT.
  Hybrid Hybridomics, 23, 244-249.  
12499636 H.Haruyama, S.Ito, K.Miyadai, T.Takahashi, R.Kawaida, T.Takayama, H.Hanzawa, T.Hata, J.Yamaguchi, H.Yoshida-Kato, K.Ichikawa, J.Ohsumi, S.Yonehara, and N.Serizawa (2002).
Humanization of the mouse anti-Fas antibody HFE7A and crystal structure of the humanized HFE7A Fab fragment.
  Biol Pharm Bull, 25, 1537-1545.
PDB code: 1it9
11248693 A.Schmidt, D.Müller, M.Mersmann, T.Wüest, E.Gerlach, P.Garin-Chesa, W.J.Rettig, K.Pfizenmaier, and D.Moosmayer (2001).
Generation of human high-affinity antibodies specific for the fibroblast activation protein by guided selection.
  Eur J Biochem, 268, 1730-1738.  
10223295 M.H.Seto, H.L.Liu, D.A.Zajchowski, and M.Whitlow (1999).
Protein fold analysis of the B30.2-like domain.
  Proteins, 35, 235-249.  
  10439113 S.Odani, Y.Komori, and F.Gejyo (1999).
Structural analysis of the amyloidogenic kappa Bence Jones protein (FUR).
  Amyloid, 6, 77-88.  
10398393 Z.C.Fan, L.Shan, B.Z.Goldsteen, L.W.Guddat, A.Thakur, N.F.Landolfi, M.S.Co, M.Vasquez, C.Queen, P.A.Ramsland, and A.B.Edmundson (1999).
Comparison of the three-dimensional structures of a humanized and a chimeric Fab of an anti-gamma-interferon antibody.
  J Mol Recognit, 12, 19-32.
PDB codes: 1b2w 1b4j
9602365 G.D.Wiens, V.A.Roberts, E.A.Whitcomb, T.O'Hare, M.P.Stenzel-Poore, and M.B.Rittenberg (1998).
Harmful somatic mutations: lessons from the dark side.
  Immunol Rev, 162, 197-209.  
9099717 M.Baca, L.G.Presta, S.J.O'Connor, and J.A.Wells (1997).
Antibody humanization using monovalent phage display.
  J Biol Chem, 272, 10678-10684.  
9329081 M.J.Banfield, D.J.King, A.Mountain, and R.L.Brady (1997).
VL:VH domain rotations in engineered antibodies: crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs.
  Proteins, 29, 161-171.
PDB codes: 1ad0 1ad9 1ae6 1clo
8647813 S.Chacko, E.A.Padlan, S.Portolano, S.M.McLachlan, and B.Rapoport (1996).
Structural studies of human autoantibodies. Crystal structure of a thyroid peroxidase autoantibody Fab.
  J Biol Chem, 271, 12191-12198.
PDB code: 1vge
  7796805 C.Chen, V.A.Roberts, S.Stevens, M.Brown, M.P.Stenzel-Poore, and M.B.Rittenberg (1995).
Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations.
  EMBO J, 14, 2784-2794.  
8524873 H.D.Ulrich, P.A.Patten, P.L.Yang, F.E.Romesberg, and P.G.Schultz (1995).
Expression studies of catalytic antibodies.
  Proc Natl Acad Sci U S A, 92, 11907-11911.  
  7556106 I.M.Tomlinson, J.P.Cox, E.Gherardi, A.M.Lesk, and C.Chothia (1995).
The structural repertoire of the human V kappa domain.
  EMBO J, 14, 4628-4638.  
7877976 J.W.Park, K.Hong, P.Carter, H.Asgari, L.Y.Guo, G.A.Keller, C.Wirth, R.Shalaby, C.Kotts, and W.I.Wood (1995).
Development of anti-p185HER2 immunoliposomes for cancer therapy.
  Proc Natl Acad Sci U S A, 92, 1327-1331.  
7536111 I.A.Wilson, and R.L.Stanfield (1994).
Antibody-antigen interactions: new structures and new conformational changes.
  Curr Opin Struct Biol, 4, 857-867.  
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.