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PDBsum entry 1eap
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Catalytic antibody PDB id
1eap

 

 

 

 

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Contents
Protein chains
213 a.a. *
216 a.a. *
Ligands
HEP
* Residue conservation analysis
PDB id:
1eap
Name: Catalytic antibody
Title: Crystal structure of a catalytic antibody with a serine protease active site
Structure: Igg2b-kappa 17e8 fab (light chain). Chain: a. Igg2b-kappa 17e8 fab (heavy chain). Chain: b
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.186    
Authors: G.W.Zhou,J.Guo,W.Huang,T.S.Scanlan,R.J.Fletterick
Key ref: G.W.Zhou et al. (1994). Crystal structure of a catalytic antibody with a serine protease active site. Science, 265, 1059-1064. PubMed id: 8066444 DOI: 10.1126/science.8066444
Date:
10-Aug-94     Release date:   20-Dec-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 213 a.a.
Protein chain
No UniProt id for this chain
Struc: 216 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1126/science.8066444 Science 265:1059-1064 (1994)
PubMed id: 8066444  
 
 
Crystal structure of a catalytic antibody with a serine protease active site.
G.W.Zhou, J.Guo, W.Huang, R.J.Fletterick, T.S.Scanlan.
 
  ABSTRACT  
 
The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution. The antibody (17E8) catalyzes the hydrolysis of norleucine and methionine phenyl esters and is selective for amino acid esters that have the natural alpha-carbon L configuration. A plot of the pH-dependence of the antibody-catalyzed reaction is bell-shaped with an activity maximum at pH 9.5; experiments on mechanism lend support to the formation of a covalent acyl-antibody intermediate. The structural and kinetic data are complementary and support a hydrolytic mechanism for the antibody that is remarkably similar to that of the serine proteases. The antibody active site contains a Ser-His dyad structure proximal to the phosphorous atom of the bound hapten that resembles two of the three components of the Ser-His-Asp catalytic triad of serine proteases. The antibody active site also contains a Lys residue to stabilize oxyanion formation, and a hydrophobic binding pocket for specific substrate recognition of norleucine and methionine side chains. The structure identifies active site residues that mediate catalysis and suggests specific mutations that may improve the catalytic efficiency of the antibody. This high resolution structure of a catalytic antibody-hapten complex shows that antibodies can converge on active site structures that have arisen through natural enzyme evolution.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20623068 Y.Gao, F.Zhao, Q.Wang, Y.Zhang, and B.Xu (2010).
Small peptide nanofibers as the matrices of molecular hydrogels for mimicking enzymes and enhancing the activity of enzymes.
  Chem Soc Rev, 39, 3425-3433.  
19099081 S.A.Beaton, M.P.Huestis, A.Sadeghi-Khomami, N.R.Thomas, and D.L.Jakeman (2009).
Enzyme-catalyzed synthesis of isosteric phosphono-analogues of sugar nucleotides.
  Chem Commun (Camb), (), 238-240.  
18044899 A.V.Reshetnyak, M.F.Armentano, N.A.Ponomarenko, D.Vizzuso, O.M.Durova, R.Ziganshin, M.Serebryakova, V.Govorun, G.Gololobov, H.C.Morse, A.Friboulet, S.P.Makker, A.G.Gabibov, and A.Tramontano (2007).
Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.
  J Am Chem Soc, 129, 16175-16182.  
16838382 Y.Nishiyama, S.Karle, Y.Mitsuda, H.Taguchi, S.Planque, M.Salas, C.Hanson, and S.Paul (2006).
Towards irreversible HIV inactivation: stable gp120 binding by nucleophilic antibodies.
  J Mol Recognit, 19, 423-431.  
17051161 Y.Wang, Y.Zhang, and Y.Ha (2006).
Crystal structure of a rhomboid family intramembrane protease.
  Nature, 444, 179-180.
PDB code: 2ic8
15361936 C.I.Chang, S.Pili-Floury, M.Hervé, C.Parquet, Y.Chelliah, B.Lemaitre, D.Mengin-Lecreulx, and J.Deisenhofer (2004).
A Drosophila pattern recognition receptor contains a peptidoglycan docking groove and unusual L,D-carboxypeptidase activity.
  PLoS Biol, 2, E277.
PDB code: 1s2j
12794866 H.Wade, and T.S.Scanlan (2003).
Binding and catalysis: a thermodynamic study on a catalytic antibody system.
  Chembiochem, 4, 537-540.  
12868101 L.T.Chong, P.Bandyopadhyay, T.S.Scanlan, I.D.Kuntz, and P.A.Kollman (2003).
Direct hydroxide attack is a plausible mechanism for amidase antibody 43C9.
  J Comput Chem, 24, 1371-1377.  
11913392 D.J.Tantillo, and K.N.Houk (2002).
Transition state docking: a probe for noncovalent catalysis in biological systems. Application to antibody-catalyzed ester hydrolysis.
  J Comput Chem, 23, 84-95.  
11933071 E.Vargas-Madrazo, and E.Paz-García (2002).
Modifications to canonical structure sequence patterns: analysis for L1 and L3.
  Proteins, 47, 250-254.  
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.  
11468416 T.A.Muranova, S.N.Ruzheinikov, S.E.Sedelnikova, A.Moir, L.J.Partridge, H.Kakinuma, N.Takahashi, K.Shimazaki, J.Sun, Y.Nishi, and D.W.Rice (2001).
The preparation and crystallization of Fab fragments of a family of mouse esterolytic catalytic antibodies and their complexes with a transition-state analogue.
  Acta Crystallogr D Biol Crystallogr, 57, 1192-1195.  
11575776 T.Tsumuraya, N.Takazawa, A.Tsunakawa, R.Fleck, and S.Masamune (2001).
Catalytic antibodies induced by a zwitterionic hapten.
  Chemistry, 7, 3748-3755.  
11095704 A.V.Kolesnikov, A.V.Kozyr, E.S.Alexandrova, F.Koralewski, A.V.Demin, M.I.Titov, B.Avalle, A.Tramontano, S.Paul, D.Thomas, A.G.Gabibov, and A.Friboulet (2000).
Enzyme mimicry by the antiidiotypic antibody approach.
  Proc Natl Acad Sci U S A, 97, 13526-13531.  
10619850 C.Birghan, E.Mundt, and A.E.Gorbalenya (2000).
A non-canonical lon proteinase lacking the ATPase domain employs the ser-Lys catalytic dyad to exercise broad control over the life cycle of a double-stranded RNA virus.
  EMBO J, 19, 114-123.  
10966475 D.Hilvert (2000).
Critical analysis of antibody catalysis.
  Annu Rev Biochem, 69, 751-793.  
11093161 S.N.Seal, M.Monestier, and M.Z.Radic (2000).
Diverse roles for the third complementarity determining region of the heavy chain (H3) in the binding of immunoglobulin Fv fragments to DNA, nucleosomes and cardiolipin.
  Eur J Immunol, 30, 3432-3440.  
11131157 Y.Li, Y.Zhao, S.Hatfield, R.Wan, Q.Zhu, X.Li, M.McMills, Y.Ma, J.Li, K.L.Brown, C.He, F.Liu, and X.Chen (2000).
Dipeptide seryl-histidine and related oligopeptides cleave DNA, protein, and a carboxyl ester.
  Bioorg Med Chem, 8, 2675-2680.  
10102985 H.Czapinska, and J.Otlewski (1999).
Structural and energetic determinants of the S1-site specificity in serine proteases.
  Eur J Biochem, 260, 571-595.  
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.  
  10595527 P.Wirtz, and B.Steipe (1999).
Intrabody construction and expression III: engineering hyperstable V(H) domains.
  Protein Sci, 8, 2245-2250.  
10214693 B.Avalle, V.Zanin, D.Thomas, and A.Friboulet (1998).
Antibody catalysis based on functional mimicry.
  Appl Biochem Biotechnol, 75, 3.  
9592396 I.Fujii, S.Fukuyama, Y.Iwabuchi, and R.Tanimura (1998).
Evolving catalytic antibodies in a phage-displayed combinatorial library.
  Nat Biotechnol, 16, 463-467.  
9770525 R.Murali, D.J.Sharkey, J.L.Daiss, and H.M.Murthy (1998).
Crystal structure of Taq DNA polymerase in complex with an inhibitory Fab: the Fab is directed against an intermediate in the helix-coil dynamics of the enzyme.
  Proc Natl Acad Sci U S A, 95, 12562-12567.
PDB code: 1bgx
9359117 A.Persidis (1997).
Catalytic antibodies. Some companies are taking an active interest in this promising technology.
  Nat Biotechnol, 15, 1313-1315.  
9208940 B.Gigant, J.B.Charbonnier, B.Golinelli-Pimpaneau, R.R.Zemel, Z.Eshhar, B.S.Green, and M.Knossow (1997).
Mechanism of inactivation of a catalytic antibody by p-nitrophenyl esters.
  Eur J Biochem, 246, 471-476.  
9223277 B.Gigant, J.B.Charbonnier, Z.Eshhar, B.S.Green, and M.Knossow (1997).
X-ray structures of a hydrolytic antibody and of complexes elucidate catalytic pathway from substrate binding and transition state stabilization through water attack and product release.
  Proc Natl Acad Sci U S A, 94, 7857-7861.
PDB codes: 1yef 1yeg 1yeh
9241427 H.Wade, and T.S.Scanlan (1997).
The structural and functional basis of antibody catalysis.
  Annu Rev Biophys Biomol Struct, 26, 461-493.  
9027317 J.B.Charbonnier, B.Golinelli-Pimpaneau, B.Gigant, D.S.Tawfik, R.Chap, D.G.Schindler, S.H.Kim, B.S.Green, Z.Eshhar, and M.Knossow (1997).
Structural convergence in the active sites of a family of catalytic antibodies.
  Science, 275, 1140-1142.
PDB codes: 1yec 1yed 1yee
9294163 M.Baca, T.S.Scanlan, R.C.Stephenson, and J.A.Wells (1997).
Phage display of a catalytic antibody to optimize affinity for transition-state analog binding.
  Proc Natl Acad Sci U S A, 94, 10063-10068.  
9096314 X.Qiu, C.A.Janson, J.S.Culp, S.B.Richardson, C.Debouck, W.W.Smith, and S.S.Abdel-Meguid (1997).
Crystal structure of varicella-zoster virus protease.
  Proc Natl Acad Sci U S A, 94, 2874-2879.
PDB code: 1vzv
8807874 G.MacBeath, and D.Hilvert (1996).
Hydrolytic antibodies: variations on a theme.
  Chem Biol, 3, 433-445.  
8643580 L.C.Hsieh-Wilson, P.G.Schultz, and R.C.Stevens (1996).
Insights into antibody catalysis: structure of an oxygenation catalyst at 1.9-angstrom resolution.
  Proc Natl Acad Sci U S A, 93, 5363-5367.
PDB codes: 1kel 1kem
8524836 J.B.Charbonnier, E.Carpenter, B.Gigant, B.Golinelli-Pimpaneau, Z.Eshhar, B.S.Green, and M.Knossow (1995).
Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies.
  Proc Natl Acad Sci U S A, 92, 11721-11725.
PDB code: 1kno
7878042 J.Guo, W.Huang, G.W.Zhou, R.J.Fletterick, and T.S.Scanlan (1995).
Mechanistically different catalytic antibodies obtained from immunization with a single transition-state analog.
  Proc Natl Acad Sci U S A, 92, 1694-1698.  
  7795518 J.J.Perona, and C.S.Craik (1995).
Structural basis of substrate specificity in the serine proteases.
  Protein Sci, 4, 337-360.
PDB code: 1amh
8749371 J.R.Jacobsen, and P.G.Schultz (1995).
The scope of antibody catalysis.
  Curr Opin Struct Biol, 5, 818-824.  
  7613462 S.C.Bagley, and R.B.Altman (1995).
Characterizing the microenvironment surrounding protein sites.
  Protein Sci, 4, 622-635.  
7773790 Y.Wei, J.L.Schottel, U.Derewenda, L.Swenson, S.Patkar, and Z.S.Derewenda (1995).
A novel variant of the catalytic triad in the Streptomyces scabies esterase.
  Nat Struct Biol, 2, 218-223.
PDB codes: 1esc 1esd 1ese
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.

 

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