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PDBsum entry 1gaf
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Catalytic antibody PDB id
1gaf

 

 

 

 

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Contents
Protein chains
214 a.a. *
217 a.a. *
Ligands
NPE
Waters ×453
* Residue conservation analysis
PDB id:
1gaf
Name: Catalytic antibody
Title: 48g7 hybridoma line fab complexed with hapten 5-(para-nitrophenyl phosphonate)-pentanoic acid
Structure: Chimeric 48g7 fab. Chain: l. Fragment: variable domains of light and heavy chains and constant domains of light and heavy chains. Engineered: yes. Other_details: both fab chains are derived from the mature (hybridoma line) antibody. The light chain consists of the vj variable domain from mouse and thE C(kappa) constant region from human. The heavy chain consists of the vdj variable domain from mouse and thE C(h1)
Source: Fragment: constant domains of light and heavy chains. Homo sapiens. Human. Organism_taxid: 9606. Cell_line: 48g7. Expressed in: bl21. Other_details: each chain is a fusion polypeptide which is part human and part mouse. Human and part mouse
Biol. unit: Dimer (from PQS)
Resolution:
1.95Å     R-factor:   0.244     R-free:   0.307
Authors: G.J.Wedemayer,P.A.Patten,R.C.Stevens,P.G.Schultz
Key ref: P.A.Patten et al. (1996). The immunological evolution of catalysis. Science, 271, 1086-1091. PubMed id: 8599084 DOI: 10.1126/science.271.5252.1086
Date:
06-Feb-96     Release date:   11-Jul-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01834  (IGKC_HUMAN) -  Immunoglobulin kappa constant from Homo sapiens
Seq:
Struc: 		107 a.a.
214 a.a.
Protein chain
Pfam   ArchSchema ?
P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens
Seq:
Struc: 		399 a.a.
217 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1126/science.271.5252.1086 Science 271:1086-1091 (1996)
PubMed id: 8599084  
 
 
The immunological evolution of catalysis.
P.A.Patten, N.S.Gray, P.L.Yang, C.B.Marks, G.J.Wedemayer, J.J.Boniface, R.C.Stevens, P.G.Schultz.
 
  ABSTRACT  
 
The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21287614 S.E.Wong, B.D.Sellers, and M.P.Jacobson (2011).
Effects of somatic mutations on CDR loop flexibility during affinity maturation.
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20972421 H.Mao, J.J.Graziano, T.M.Chase, C.A.Bentley, O.A.Bazirgan, N.P.Reddy, B.D.Song, and V.V.Smider (2010).
Spatially addressed combinatorial protein libraries for recombinant antibody discovery and optimization.
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20149744 N.S.Greenspan (2010).
Cohen's Conjecture, Howard's Hypothesis, and Ptashne's Ptruth: an exploration of the relationship between affinity and specificity.
  Trends Immunol, 31, 138-143.  
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.
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17720880 M.Forconi, J.A.Piccirilli, and D.Herschlag (2007).
Modulation of individual steps in group I intron catalysis by a peripheral metal ion.
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16954202 J.Zimmermann, E.L.Oakman, I.F.Thorpe, X.Shi, P.Abbyad, C.L.Brooks, S.G.Boxer, and F.E.Romesberg (2006).
Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics.
  Proc Natl Acad Sci U S A, 103, 13722-13727.  
16273596 L.Otte, T.Knaute, J.Schneider-Mergener, and A.Kramer (2006).
Molecular basis for the binding polyspecificity of an anti-cholera toxin peptide 3 monoclonal antibody.
  J Mol Recognit, 19, 49-59.  
15880452 J.L.Pellequer, S.W.Chen, Y.S.Keum, A.E.Karu, Q.X.Li, and V.A.Roberts (2005).
Structural basis for preferential binding of non-ortho-substituted polychlorinated biphenyls by the monoclonal antibody S2B1.
  J Mol Recognit, 18, 282-294.  
16384106 M.C.Demirel, and A.M.Lesk (2005).
Molecular forces in antibody maturation.
  Phys Rev Lett, 95, 208106.  
15716973 M.Krogsgaard, and M.M.Davis (2005).
How T cells 'see' antigen.
  Nat Immunol, 6, 239-245.  
15640805 N.A.Borg, L.K.Ely, T.Beddoe, W.A.Macdonald, H.H.Reid, C.S.Clements, A.W.Purcell, L.Kjer-Nielsen, J.J.Miles, S.R.Burrows, J.McCluskey, and J.Rossjohn (2005).
The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition.
  Nat Immunol, 6, 171-180.  
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.  
15001706 R.Jimenez, G.Salazar, J.Yin, T.Joo, and F.E.Romesberg (2004).
Protein dynamics and the immunological evolution of molecular recognition.
  Proc Natl Acad Sci U S A, 101, 3803-3808.  
12497602 D.B.Gordon, G.K.Hom, S.L.Mayo, and N.A.Pierce (2003).
Exact rotamer optimization for protein design.
  J Comput Chem, 24, 232-243.  
12851924 F.E.Romesberg (2003).
Multidisciplinary experimental approaches to characterizing biomolecular dynamics.
  Chembiochem, 4, 563-571.  
12483203 G.M.Süel, S.W.Lockless, M.A.Wall, and R.Ranganathan (2003).
Evolutionarily conserved networks of residues mediate allosteric communication in proteins.
  Nat Struct Biol, 10, 59-69.  
12831531 R.J.Olsen, J.Mazlo, S.A.Koepsell, T.W.McKeithan, and S.H.Hinrichs (2003).
Minimal structural elements of an inhibitory anti-ATF1/CREB single-chain antibody fragment (scFv41.4).
  Hybrid Hybridomics, 22, 65-77.  
12518056 R.Jimenez, G.Salazar, K.K.Baldridge, and F.E.Romesberg (2003).
Flexibility and molecular recognition in the immune system.
  Proc Natl Acad Sci U S A, 100, 92-97.  
14573866 U.Lamminmäki, A.Westerlund-Karlsson, M.Toivola, and P.Saviranta (2003).
Modulating the binding properties of an anti-17beta-estradiol antibody by systematic mutation combinations.
  Protein Sci, 12, 2549-2558.  
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.  
12496069 N.Sinha, S.Mohan, C.A.Lipschultz, and S.J.Smith-Gill (2002).
Differences in electrostatic properties at antibody-antigen binding sites: implications for specificity and cross-reactivity.
  Biophys J, 83, 2946-2968.  
12163066 W.P.Russ, and R.Ranganathan (2002).
Knowledge-based potential functions in protein design.
  Curr Opin Struct Biol, 12, 447-452.  
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.  
11592132 S.V.Taylor, P.Kast, and D.Hilvert (2001).
Investigating and Engineering Enzymes by Genetic Selection.
  Angew Chem Int Ed Engl, 40, 3310-3335.  
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.  
11329268 Y.Li, C.A.Lipschultz, S.Mohan, and S.J.Smith-Gill (2001).
Mutations of an epitope hot-spot residue alter rate limiting steps of antigen-antibody protein-protein associations.
  Biochemistry, 40, 2011-2022.  
11213226 A.Ramakrishnan, and A.Sadana (2000).
Analyte-receptor binding and dissociation kinetics for biosensor applications: a fractal analysis.
  Biosens Bioelectron, 15, 651-662.  
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.  
10966475 D.Hilvert (2000).
Critical analysis of antibody catalysis.
  Annu Rev Biochem, 69, 751-793.  
10933393 J.L.Xu, and M.M.Davis (2000).
Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities.
  Immunity, 13, 37-45.  
11056035 L.Choulier, V.Lafont, N.Hugo, and D.Altschuh (2000).
Covariance analysis of protein families: the case of the variable domains of antibodies.
  Proteins, 41, 475-484.  
10900265 L.O.Nilsson, A.Gustafsson, and B.Mannervik (2000).
Redesign of substrate-selectivity determining modules of glutathione transferase A1-1 installs high catalytic efficiency with toxic alkenal products of lipid peroxidation.
  Proc Natl Acad Sci U S A, 97, 9408-9412.  
10859335 M.Brown, M.A.Schumacher, G.D.Wiens, R.G.Brennan, and M.B.Rittenberg (2000).
The structural basis of repertoire shift in an immune response to phosphocholine.
  J Exp Med, 191, 2101-2112.
PDB code: 1dl7
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.  
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.  
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.  
9501184 J.Yu, S.Y.Choi, K.D.Moon, H.H.Chung, H.J.Youn, S.Jeong, H.Park, and P.G.Schultz (1998).
A glycosidase antibody elicited against a chair-like transition state analog by in vitro immunization.
  Proc Natl Acad Sci U S A, 95, 2880-2884.  
9597140 M.M.Davis, J.J.Boniface, Z.Reich, D.Lyons, J.Hampl, B.Arden, and Y.Chien (1998).
Ligand recognition by alpha beta T cell receptors.
  Annu Rev Immunol, 16, 523-544.  
9843932 P.G.Schultz (1998).
Bringing biological solutions to chemical problems.
  Proc Natl Acad Sci U S A, 95, 14590-14591.  
9667908 P.Wentworth, and K.D.Janda (1998).
Catalytic antibodies.
  Curr Opin Chem Biol, 2, 138-144.  
9928017 S.Paul (1998).
Autoantibody catalysis: no longer hostage to Occam's razor.
  Ann N Y Acad Sci, 865, 238-246.  
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
9265726 D.B.Smithrud, and S.J.Benkovic (1997).
The state of antibody catalysis.
  Curr Opin Biotechnol, 8, 459-466.  
9294168 D.R.Liu, T.J.Magliery, M.Pastrnak, and P.G.Schultz (1997).
Engineering a tRNA and aminoacyl-tRNA synthetase for the site-specific incorporation of unnatural amino acids into proteins in vivo.
  Proc Natl Acad Sci U S A, 94, 10092-10097.  
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
9176702 J.G.Cyster (1997).
Signaling thresholds and interclonal competition in preimmune B-cell selection.
  Immunol Rev, 156, 87.  
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.  
9241429 P.Schuck (1997).
Use of surface plasmon resonance to probe the equilibrium and dynamic aspects of interactions between biological macromolecules.
  Annu Rev Biophys Biomol Struct, 26, 541-566.  
9667889 S.J.Rowan, and J.K.Sanders (1997).
Enzyme models: design and selection.
  Curr Opin Chem Biol, 1, 483-490.  
8939683 D.H.Williams, and M.S.Westwell (1996).
Weak interactions and lessons from crystallization.
  Chem Biol, 3, 695-701.  
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
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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