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PDBsum entry 1sm3
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protein ligands metals Protein-protein interface(s) links
Complex (antibody/peptide epitope) PDB id
1sm3

 

 

 

 

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Contents
Protein chains
210 a.a. *
211 a.a. *
Ligands
SER-ALA-PRO-ASP-
THR-ARG-PRO-ALA-
PRO
Metals
_CD ×8
_CL ×2
Waters ×331
* Residue conservation analysis
PDB id:
1sm3
Name: Complex (antibody/peptide epitope)
Title: Crystal structure of the tumor specific antibody sm3 complex with its peptide epitope
Structure: Sm3 antibody. Chain: l. Fragment: fab fragment. Sm3 antibody. Chain: h. Fragment: fab fragment. Peptide epitope. Chain: p. Engineered: yes.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organ: breast. Tissue: epithelial.
Biol. unit: Trimer (from PQS)
Resolution:
1.95Å     R-factor:   0.213     R-free:   0.283
Authors: P.Dokurno,P.A.Bates,H.A.Band,L.M.D.Stewart,J.M.Lally,J.M.Burchell, J.Taylor-Papadimitriou,M.J.E.Sternberg,D.Snary,P.S.Freemont
Key ref:
P.Dokurno et al. (1998). Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition. J Mol Biol, 284, 713-728. PubMed id: 9826510 DOI: 10.1006/jmbi.1998.2209
Date:
23-Dec-97     Release date:   23-Mar-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01723  (LV1A_MOUSE) -  Ig lambda-1 chain V region from Mus musculus
Seq:
Struc: 		117 a.a.
210 a.a.*
Protein chain
Pfam   ArchSchema ?
P01801  (HVM32_MOUSE) -  Ig heavy chain V-III region J606 from Mus musculus
Seq:
Struc: 		115 a.a.
211 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 

 
DOI no: 10.1006/jmbi.1998.2209 J Mol Biol 284:713-728 (1998)
PubMed id: 9826510  
 
 
Crystal structure at 1.95 A resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition.
P.Dokurno, P.A.Bates, H.A.Band, L.M.Stewart, J.M.Lally, J.M.Burchell, J.Taylor-Papadimitriou, D.Snary, M.J.Sternberg, P.S.Freemont.
 
  ABSTRACT  
 
The anti-breast tumour antibody SM3 has a high selectivity in reacting specifically with carcinoma-associated mucin. SM3 recognises the core repeating motif (Pro-Asp-Thr-Arg-Pro) of aberrantly glycosylated epithelial mucin MUC1, and has potential as a therapeutic and diagnostic tool. Here we report the crystal structure of the Fab fragment of SM3 in complex with a 13-residue MUC1 peptide antigen (Thr1P-Ser2P-Ala3P-Pro4P-Asp5P-Thr6P -Arg7P-Pro8P-Ala9P-Pro10P-Gly11P- Ser12P-Thr13P). The SM3-MUC1 peptide structure was solved by molecular replacement, and the current model is refined at 1.95 A resolution with an R-factor of 21.3% and R-free 28.3%. The MUC1 peptide is bound both by non-polar interactions and hydrogen bonds in an elongated groove in the antibody-combining site through interactions with Complimentarity Determining Regions (CDRs), three of the light chain (L1, L2, L3) and two of the heavy chain (H1 and H3). The conformation of the peptide is mainly extended with no discernable standard secondary structure. There is a single non-proline cis-peptide bond in H3 (Val95H-Gly96H-Gln97H-Phe98H-Ala101H-Ty r102H) between Gly96H and Gln97H, which appears to play a role in SM3-peptide antigen interactions, and represents the first such example within an antibody hypervariable loop. The SM3-MUC1 peptide structure has implications for rational therapeutic and diagnostic antibody engineering.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Amino acid sequences of the SM3 Fab V[L] and V[H], and the peptide from MUC1 mucin used in this study. Numbering and CDRs (underlined) are defined according to [Kabat et al 1991]. 		Figure 8.
Figure 8. Stereo view of the MUC1 peptide in the antibody combining site. The peptide antigen is labelled and is shown in bold. SM3 Fab residues which interact with the peptide are labelled (see Table 4). Hydrogen bonds are shown as broken lines with water molecules as black spheres. Drawn by MOLSCRIPT [Kraulis 1991].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 284, 713-728) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21451866 F.Corzana, J.H.Busto, F.Marcelo, M.García de Luis, J.L.Asensio, S.Martín-Santamaría, Y.Sáenz, C.Torres, J.Jiménez-Barbero, A.Avenoza, and J.M.Peregrina (2011).
Rational design of a Tn antigen mimic.
  Chem Commun (Camb), 47, 5319-5321.  
21305012 W.C.Chiu, Y.P.Lai, and M.Y.Chou (2011).
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody.
  PLoS One, 6, e16373.  
20479270 C.L.Brooks, A.Schietinger, S.N.Borisova, P.Kufer, M.Okon, T.Hirama, C.R.Mackenzie, L.X.Wang, H.Schreiber, and S.V.Evans (2010).
Antibody recognition of a unique tumor-specific glycopeptide antigen.
  Proc Natl Acad Sci U S A, 107, 10056-10061.
PDB codes: 3iet 3if1
18158739 S.Paul, M.Geist, K.Dott, D.Snary, J.Taylor-Papadimitriou, B.Acres, N.Silvestre, M.P.Kieny, and J.M.Balloul (2007).
Specific Tumor Cell Targeting by a Recombinant MVA Expressing a Functional Single Chain Antibody on the Surface of Intracellular Mature Virus (IMV) Particles.
  Viral Immunol, 20, 664-672.  
16269547 T.A.Sulchek, R.W.Friddle, K.Langry, E.Y.Lau, H.Albrecht, T.V.Ratto, S.J.DeNardo, M.E.Colvin, and A.Noy (2005).
Dynamic force spectroscopy of parallel individual Mucin1-antibody bonds.
  Proc Natl Acad Sci U S A, 102, 16638-16643.  
15103154 R.K.Gaur, M.B.Kupper, R.Fischer, and K.M.Hoffmann (2004).
Preliminary X-ray analysis of a human V(H) fragment at 1.8 A resolution.
  Acta Crystallogr D Biol Crystallogr, 60, 965-967.  
12654007 M.M.Pütz, J.Hoebeke, W.Ammerlaan, S.Schneider, and C.P.Muller (2003).
Functional fine-mapping and molecular modeling of a conserved loop epitope of the measles virus hemagglutinin protein.
  Eur J Biochem, 270, 1515-1527.  
11874459 H.Möller, N.Serttas, H.Paulsen, J.M.Burchell, and J.Taylor-Papadimitriou (2002).
NMR-based determination of the binding epitope and conformational analysis of MUC-1 glycopeptides and peptides bound to the breast cancer-selective monoclonal antibody SM3.
  Eur J Biochem, 269, 1444-1455.  
12193281 P.Gangatirkar, S.Gangadharan, A.Narendranath, S.Nagpal, D.M.Salunke, and A.A.Karande (2002).
Monoclonal antibodies to gonadotropin-releasing hormone (GnRH) inhibit binding of the hormone to its receptor.
  Hybrid Hybridomics, 21, 281-286.  
11922395 S.Mitchell, P.Abel, S.Madaan, J.Jeffs, K.Chaudhary, G.Stamp, and e.l.-.N.Lalani (2002).
Androgen-dependent regulation of human MUC1 mucin expression.
  Neoplasia, 4, 9.  
11009623 L.Kirnarsky, O.Prakash, S.M.Vogen, M.Nomoto, M.A.Hollingsworth, and S.Sherman (2000).
Structural effects of O-glycosylation on a 15-residue peptide from the mucin (MUC1) core protein.
  Biochemistry, 39, 12076-12082.  
10910139 S.Paul, D.Snary, J.Hoebeke, D.Allen, J.M.Balloul, N.Bizouarne, K.Dott, M.Geist, J.Hilgers, M.P.Kieny, J.Burchell, J.Taylor-Papadimitriou, and R.B.Acres (2000).
Targeted macrophage cytotoxicity using a nonreplicative live vector expressing a tumor-specific single-chain variable region fragment.
  Hum Gene Ther, 11, 1417-1428.  
10508712 P.J.Hudson (1999).
Recombinant antibody constructs in cancer therapy.
  Curr Opin Immunol, 11, 548-557.  
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 codes are shown on the right.

 

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