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PDBsum entry 1e07

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Glycoprotein PDB id
1e07
Jmol
Contents
Protein chain
642 a.a.* *
* Residue conservation analysis
* C-alpha coords only
PDB id:
1e07
Name: Glycoprotein
Title: Model of human carcinoembryonic antigen by homology modelling and curve-fitting to experimental solution scattering data
Structure: Carcinoembryonic antigen. Chain: a
Source: Homo sapiens. Human. Organism_taxid: 9606
Authors: M.K.Boehm,S.J.Perkins
Key ref:
M.K.Boehm and S.J.Perkins (2000). Structural models for carcinoembryonic antigen and its complex with the single-chain Fv antibody molecule MFE23. FEBS Lett, 475, 11-16. PubMed id: 10854848 DOI: 10.1016/S0014-5793(00)01612-4
Date:
11-Mar-00     Release date:   04-Jul-00    
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06731  (CEAM5_HUMAN) -  Carcinoembryonic antigen-related cell adhesion molecule 5
Seq:
Struc:
 
Seq:
Struc:
702 a.a.
642 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to external side of plasma membrane   7 terms 
  Biological process     negative regulation of anoikis   4 terms 
  Biochemical function     identical protein binding     3 terms  

 

 
    Key reference    
 
 
DOI no: 10.1016/S0014-5793(00)01612-4 FEBS Lett 475:11-16 (2000)
PubMed id: 10854848  
 
 
Structural models for carcinoembryonic antigen and its complex with the single-chain Fv antibody molecule MFE23.
M.K.Boehm, S.J.Perkins.
 
  ABSTRACT  
 
MFE23 is a single chain Fv antibody that has a high affinity for carcinoembryonic antigen (CEA). A full homology model for CEA based on V-type, I-type and C2-type immunoglobulin folds, 28 oligosaccharides and the interdomain angle of CD2 was validated using solution scattering data. The superimposition of the intermolecular contacts observed in our recent crystal structure of MFE23 with the N-terminal domain of CEA permitted the MFE23-CEA complex to be modelled. Good surface and electrostatic complementarity and carbohydrate-unhindered access of MFE23 with the indentation between the first two CEA domains was observed. The model is supported by biochemical data and provides insight on the high affinity of MFE23 for CEA.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Sequence alignment used for the modelling of CEA based on homologous crystal structures. The 28 oligosaccharide sites in CEA are denoted by bold underlining. Sequences are labelled with their PDB code, and underlined regions indicate the structures used to construct the CEA homology models. The β-strands (E) identified by the DSSP program are labelled A to G. a: The V-type domain of CEA is compared with the first V-type domain in CD2, CD4 and CD8. b: The three I-type domains of CEA are compared with that found in the first domain of VCAM-1. The V-frame profile that resulted in the assignment to an I-type domain is shown asterisked above the alignment. c: The three C2-type domains of CEA are compared with that found in the second domain of the cell-surface protein CD2.
Figure 3.
Fig. 3. The predicted model of the MFE23 complex with CEA-1 and CEA-2. a: An electrostatic view of the CEA-1 and CEA-2 domains is shown, where a stripe of basic residues (Lys-15, Arg-64, Lys-112, Lys-180, Arg-190 and Arg-191) at the interface between the CEA-1 and CEA-2 domains is arrowed. b: The α-carbons of these six basic residues are shown as blue spheres in the ribbon view of the CEA homology model (V-type, yellow; I-type, green) which is rotated by 180° about the vertical axis relative to the electrostatic view of the CEA-1 and CEA-2 domains. These basic residues are complementary to a stripe of acidic residues seen on the MFE23 electrostatic surface. These acidic residues are located on the H1 and H2 loops of MFE23 and at the N-terminus of the V[L] domain, and involve Asp-H31, Asp-H52, Glu-H53, Asp-H56, Glu-H58 and Glu-L1. c: Comparison of the oligosaccharide arrangement in CEA relative to the modelled MFE23 binding site on CEA. A ribbon diagram of MFE23 (white) is shown attached to the CEA-1 and CEA-2 domains (yellow and green respectively), in which the CEA-1 and CEA-2 domains are shown in the same orientation as the two domains in a. Seven oligosaccharide chains at Asn-70 and Asn-81 in CEA-1 and at Asn-118, Asn-148, Asn-163, Asn-170 and Asn-174 in CEA-2 are shown in blue solid representations. These do not prevent MFE23 binding at the interface between the CEA-1 and CEA-2 domains.
 
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2000, 475, 11-16) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21159620 D.Bannister, B.Popovic, S.Sridharan, F.Giannotta, P.Filée, N.Yilmaz, and R.Minter (2011).
Epitope mapping and key amino acid identification of anti-CD22 immunotoxin CAT-8015 using hybrid {beta}-lactamase display.
  Protein Eng Des Sel, 24, 351-360.  
21290601 J.V.Jokerst, J.Chou, J.P.Camp, J.Wong, A.Lennart, A.A.Pollard, P.N.Floriano, N.Christodoulides, G.W.Simmons, Y.Zhou, M.F.Ali, and J.T.McDevitt (2011).
Location of Biomarkers and Reagents within Agarose Beads of a Programmable Bio-nano-chip.
  Small, 7, 613-624.  
18214466 C.Neylon (2008).
Small angle neutron and X-ray scattering in structural biology: recent examples from the literature.
  Eur Biophys J, 37, 531-541.  
18656482 H.Kogelberg, B.Tolner, G.J.Thomas, D.Di Cara, S.Minogue, B.Ramesh, S.Sodha, D.Marsh, M.W.Lowdell, T.Meyer, R.H.Begent, I.Hart, J.F.Marshall, and K.Chester (2008).
Engineering a single-chain Fv antibody to alpha v beta 6 integrin using the specificity-determining loop of a foot-and-mouth disease virus.
  J Mol Biol, 382, 385-401.  
17428798 A.Bonner, C.Perrier, B.Corthésy, and S.J.Perkins (2007).
Solution structure of human secretory component and implications for biological function.
  J Biol Chem, 282, 16969-16980.
PDB code: 2ocw
  19662225 J.M.Kneller, T.Ehlen, J.P.Matisic, D.Miller, D.Van Niekerk, W.L.Lam, M.Marra, R.Richards-Kortum, M.Follen, C.Macaulay, and S.J.Jones (2007).
Using LongSAGE to Detect Biomarkers of Cervical Cancer Potentially Amenable to Optical Contrast Agent Labelling.
  Biomark Insights, 2, 447-461.  
15838376 R.D.Guest, R.E.Hawkins, N.Kirillova, E.J.Cheadle, J.Arnold, A.O'Neill, J.Irlam, K.A.Chester, J.T.Kemshead, D.M.Shaw, M.J.Embleton, P.L.Stern, and D.E.Gilham (2005).
The role of extracellular spacer regions in the optimal design of chimeric immune receptors: evaluation of four different scFvs and antigens.
  J Immunother (1997), 28, 203-211.  
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.