PDBsum entry 1a4k

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protein ligands metals Protein-protein interface(s) links
Immunoglobulin PDB id
Protein chains
217 a.a. *
217 a.a. *
FRA ×2
_CD ×4
Waters ×213
* Residue conservation analysis
PDB id:
Name: Immunoglobulin
Title: Diels alder catalytic antibody with transition state analogue
Structure: Antibody fab. Chain: l, a. Fragment: fab. Engineered: yes. Antibody fab. Chain: h, b. Fragment: fab. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Cell_line: 25f2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Hetero-Dimer (from PDB file)
2.40Å     R-factor:   0.211     R-free:   0.291
Authors: B.W.Spiller,F.E.Romesburg,P.G.Schultz,R.C.Stevens
Key ref:
F.E.Romesberg et al. (1998). Immunological origins of binding and catalysis in a Diels-Alderase antibody. Science, 279, 1929-1933. PubMed id: 9506942 DOI: 10.1126/science.279.5358.1929
30-Jan-98     Release date:   13-May-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P01834  (IGKC_HUMAN) -  Ig kappa chain C region
106 a.a.
217 a.a.
Protein chains
No UniProt id for this chain
Struc: 217 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   5 terms 
  Biological process     Fc-epsilon receptor signaling pathway   8 terms 
  Biochemical function     antigen binding     1 term  


DOI no: 10.1126/science.279.5358.1929 Science 279:1929-1933 (1998)
PubMed id: 9506942  
Immunological origins of binding and catalysis in a Diels-Alderase antibody.
F.E.Romesberg, B.Spiller, P.G.Schultz, R.C.Stevens.
The three-dimensional structure of an antibody (39-A11) that catalyzes a Diels-Alder reaction has been determined. The structure suggests that the antibody catalyzes this pericyclic reaction through a combination of packing and hydrogen-bonding interactions that control the relative geometries of the bound substrates and electronic distribution in the dienophile. A single somatic mutation, serine-91 of the light chain to valine, is largely responsible for the increase in affinity and catalytic activity of the affinity-matured antibody. Structural and functional studies of the germ-line precursor suggest that 39-A11 and related antibodies derive from a family of germ-line genes that have been selected throughout evolution for the ability of the encoded proteins to form a polyspecific combining site. Germ line-encoded antibodies of this type, which can rapidly evolve into high-affinity receptors for a broad range of structures, may help to expand the binding potential associated with the structural diversity of the primary antibody repertoire.
  Selected figure(s)  
Figure 3.
Fig. 3. Structures of ligands used in binding assays with 39-A11 and its germ-line precursor.
Figure 4.
Fig. 4. Superposition of the CDRL3 and CDRH3 loops of antibodies DB3, TE33, and 39-A11 with bound steroid (green), peptide (blue), and hapten 4 (purple), respectively. TrpH50, Asn/SerH35, and Trp/ArgH100 are also shown.
  The above figures are reprinted by permission from the AAAs: Science (1998, 279, 1929-1933) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21298133 R.A.Lerner (2011).
Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire.
  Mol Biosyst, 7, 1004-1012.  
21173256 H.N.Eisen, and A.K.Chakraborty (2010).
Evolving concepts of specificity in immune reactions.
  Proc Natl Acad Sci U S A, 107, 22373-22380.  
19301315 C.Li, K.E.Roege, and W.L.Kelly (2009).
Analysis of the indanomycin biosynthetic gene cluster from Streptomyces antibioticus NRRL 8167.
  Chembiochem, 10, 1064-1072.  
19304744 K.T.Gagnon, S.Y.Ju, M.B.Goshe, E.S.Maxwell, and S.Franzen (2009).
A role for hydrophobicity in a Diels-Alder reaction catalyzed by pyridyl-modified RNA.
  Nucleic Acids Res, 37, 3074-3082.  
19801545 V.Sharma, W.Heriot, K.Trisler, and V.Smider (2009).
A human germ line antibody light chain with hydrolytic properties associated with multimerization status.
  J Biol Chem, 284, 33079-33087.  
19039353 W.L.Kelly (2008).
Intramolecular cyclizations of polyketide biosynthesis: mining for a "Diels-Alderase"?
  Org Biomol Chem, 6, 4483-4493.  
17457413 J.M.Serafimov, H.C.Lehmann, H.Oikawa, and D.Hilvert (2007).
Active site mutagenesis of the putative Diels-Alderase macrophomate synthase.
  Chem Commun (Camb), (), 1701-1703.  
16618601 D.K.Sethi, A.Agarwal, V.Manivel, K.V.Rao, and D.M.Salunke (2006).
Differential epitope positioning within the germline antibody paratope enhances promiscuity in the primary immune response.
  Immunity, 24, 429-438.  
16528766 M.T.Reetz, and N.Jiao (2006).
Copper-phthalocyanine conjugates of serum albumins as enantioselective catalysts in Diels-Alder reactions.
  Angew Chem Int Ed Engl, 45, 2416-2419.  
15723077 A.Serganov, S.Keiper, L.Malinina, V.Tereshko, E.Skripkin, C.Höbartner, A.Polonskaia, A.T.Phan, R.Wombacher, R.Micura, Z.Dauter, A.Jäschke, and D.J.Patel (2005).
Structural basis for Diels-Alder ribozyme-catalyzed carbon-carbon bond formation.
  Nat Struct Mol Biol, 12, 218-224.
PDB codes: 1ykq 1ykv 1yls
16003810 V.Gouverneur, and M.Reiter (2005).
Biocatalytic approaches to hetero-Diels-Alder adducts of carbonyl compounds.
  Chemistry, 11, 5806-5815.  
16094605 V.N.Uversky, C.J.Oldfield, and A.K.Dunker (2005).
Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling.
  J Mol Recognit, 18, 343-384.  
15286657 A.Macchiarulo, I.Nobeli, and J.M.Thornton (2004).
Ligand selectivity and competition between enzymes in silico.
  Nat Biotechnol, 22, 1039-1045.  
15185369 A.Piatesi, and D.Hilvert (2004).
Immunological optimization of a generic hydrophobic pocket for high affinity hapten binding and Diels-Alder activity.
  Chembiochem, 5, 460-466.  
15213379 T.Ose, K.Watanabe, M.Yao, M.Honma, H.Oikawa, and I.Tanaka (2004).
Structure of macrophomate synthase.
  Acta Crystallogr D Biol Crystallogr, 60, 1187-1197.  
12851924 F.E.Romesberg (2003).
Multidisciplinary experimental approaches to characterizing biomolecular dynamics.
  Chembiochem, 4, 563-571.  
12634789 T.Ose, K.Watanabe, T.Mie, M.Honma, H.Watanabe, M.Yao, H.Oikawa, and I.Tanaka (2003).
Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase.
  Nature, 422, 185-189.
PDB code: 1izc
12093912 M.Hugot, N.Bensel, M.Vogel, M.T.Reymond, B.Stadler, J.L.Reymond, and U.Baumann (2002).
A structural basis for the activity of retro-Diels-Alder catalytic antibodies: evidence for a catalytic aromatic residue.
  Proc Natl Acad Sci U S A, 99, 9674-9678.
PDB codes: 1lo0 1lo2 1lo3 1lo4
11688715 A.Jäschke (2001).
RNA-catalyzed carbon-carbon bond formation.
  Biol Chem, 382, 1321-1325.  
11410373 D.J.Tantillo, and K.N.Houk (2001).
Canonical binding arrays as molecular recognition elements in the immune system: tetrahedral anions and the ester hydrolysis transition state.
  Chem Biol, 8, 535-545.  
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.  
10651626 E.C.Mundorff, M.A.Hanson, A.Varvak, H.Ulrich, P.G.Schultz, and R.C.Stevens (2000).
Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement.
  Biochemistry, 39, 627-632.
PDB codes: 1d5b 1d5i 1d6v
10535917 B.Spiller, A.Gershenson, F.H.Arnold, and R.C.Stevens (1999).
A structural view of evolutionary divergence.
  Proc Natl Acad Sci U S A, 96, 12305-12310.
PDB codes: 1c00 1c7i 1c7j 1qe3 1qe8
10588705 L.T.Chong, Y.Duan, L.Wang, I.Massova, and P.A.Kollman (1999).
Molecular dynamics and free-energy calculations applied to affinity maturation in antibody 48G7.
  Proc Natl Acad Sci U S A, 96, 14330-14335.  
10449375 R.W.Roberts, and W.W.Ja (1999).
In vitro selection of nucleic acids and proteins: What are we learning?
  Curr Opin Struct Biol, 9, 521-529.  
10585916 W.Radding, T.Romo, and G.N.Phillips (1999).
Protein-assisted pericyclic reactions: an alternate hypothesis for the action of quantal receptors.
  Biophys J, 77, 2920-2929.  
9724736 H.Pedersen, S.Hölder, D.P.Sutherlin, U.Schwitter, D.S.King, and P.G.Schultz (1998).
A method for directed evolution and functional cloning of enzymes.
  Proc Natl Acad Sci U S A, 95, 10523-10528.  
9843932 P.G.Schultz (1998).
Bringing biological solutions to chemical problems.
  Proc Natl Acad Sci U S A, 95, 14590-14591.  
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.