PDBsum entry 1kir

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protein Protein-protein interface(s) links
Complex (immunoglobulin/hydrolase) PDB id
Protein chains
107 a.a. *
116 a.a. *
129 a.a. *
Waters ×142
* Residue conservation analysis
PDB id:
Name: Complex (immunoglobulin/hydrolase)
Title: Fv mutant y(a 50)s (vl domain) of mouse monoclonal antibody d1.3 complexed with hen egg white lysozyme
Structure: Monoclonal antibody d1.3. Chain: a. Engineered: yes. Mutation: yes. Monoclonal antibody d1.3. Chain: b. Engineered: yes. Mutation: yes. Lysozyme.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organ: egg. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031.
Biol. unit: Trimer (from PQS)
2.00Å     R-factor:   0.167    
Authors: B.A.Fields,R.J.Poljak,R.A.Mariuzza
Key ref:
B.A.Fields et al. (1996). Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme. Biochemistry, 35, 15494-15503. PubMed id: 8952503 DOI: 10.1021/bi961709e
23-Oct-96     Release date:   23-Dec-96    
Go to PROCHECK summary

Protein chain
No UniProt id for this chain
Struc: 107 a.a.
Protein chain
Pfam   ArchSchema ?
P01820  (HVM44_MOUSE) -  Ig heavy chain V region PJ14
115 a.a.
116 a.a.*
Protein chain
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
147 a.a.
129 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain C: E.C.  - Lysozyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     7 terms  


DOI no: 10.1021/bi961709e Biochemistry 35:15494-15503 (1996)
PubMed id: 8952503  
Hydrogen bonding and solvent structure in an antigen-antibody interface. Crystal structures and thermodynamic characterization of three Fv mutants complexed with lysozyme.
B.A.Fields, F.A.Goldbaum, W.Dall'Acqua, E.L.Malchiodi, A.Cauerhff, F.P.Schwarz, X.Ysern, R.J.Poljak, R.A.Mariuzza.
Using site-directed mutagenesis, X-ray crystallography, and titration calorimetry, we have examined the structural and thermodynamic consequences of removing specific hydrogen bonds in an antigen-antibody interface. Crystal structures of three antibody FvD1.3 mutants, VLTyr50Ser (VLY50S), VHTyr32Ala (VHY32A), and VHTyr101Phe (VHY101F), bound to hen egg white lysozyme (HEL) have been determined at resolutions ranging from 1.85 to 2.10 A. In the wild-type (WT) FvD1.3-HEL complex, the hydroxyl groups of VLTyr50, VHTyr32, and VHTyr101 each form at least one hydrogen bond with the lysozyme antigen. Thermodynamic parameters for antibody-antigen association have been measured using isothermal titration calorimetry, giving equilibrium binding constants Kb (M-1) of 2.6 x 10(7) (VLY50S), 7.0 x 10(7) (VHY32A), and 4.0 x 10(6) (VHY101F). For the WT complex, Kb is 2.7 x 10(8) M-1; thus, the affinities of the mutant Fv fragments for HEL are 10-, 4-, and 70-fold lower than that of the original antibody, respectively. In all three cases entropy compensation results in an affinity loss that would otherwise be larger. Comparison of the three mutant crystal structures with the WT structure demonstrates that the removal of direct antigen-antibody hydrogen bonds results in minimal shifts in the positions of the remaining protein atoms. These observations show that this complex is considerably tolerant, both structurally and thermodynamically, to the truncation of antibody side chains that form hydrogen bonds with the antigen. Alterations in interface solvent structure for two of the mutant complexes (VLY50S and VHY32A) appear to compensate for the unfavorable enthalpy changes when protein-protein interactions are removed. These changes in solvent structure, along with the increased mobility of side chains near the mutation site, probably contribute to the observed entropy compensation. For the VHY101F complex, the nature of the large entropy compensation is not evident from a structural comparison of the WT and mutant complexes. Differences in the local structure and dynamics of the uncomplexed Fv molecules may account for the entropic discrepancy in this case.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20038580 A.Yokota, K.Tsumoto, M.Shiroishi, T.Nakanishi, H.Kondo, and I.Kumagai (2010).
Contribution of asparagine residues to the stabilization of a proteinaceous antigen-antibody complex, HyHEL-10-hen egg white lysozyme.
  J Biol Chem, 285, 7686-7696.
PDB codes: 3a67 3a6b 3a6c
18326040 K.Tsumoto, A.Yokota, Y.Tanaka, M.Ui, T.Tsumuraya, I.Fujii, I.Kumagai, Y.Nagumo, H.Oguri, M.Inoue, and M.Hirama (2008).
Critical contribution of aromatic rings to specific recognition of polyether rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49.
  J Biol Chem, 283, 12259-12266.
PDB code: 2e27
17166830 M.Shiroishi, K.Tsumoto, Y.Tanaka, A.Yokota, T.Nakanishi, H.Kondo, and I.Kumagai (2007).
Structural consequences of mutations in interfacial Tyr residues of a protein antigen-antibody complex. The case of HyHEL-10-HEL.
  J Biol Chem, 282, 6783-6791.
PDB codes: 2dqc 2dqd 2dqe 2dqf 2dqg 2dqh 2dqi 2dqj
16284258 P.Monecke, T.Borosch, J.Brickmann, and S.M.Kast (2006).
Determination of the interfacial water content in protein-protein complexes from free energy simulations.
  Biophys J, 90, 841-850.  
17145365 R.J.Duquesnoy (2006).
A structurally based approach to determine HLA compatibility at the humoral immune level.
  Hum Immunol, 67, 847-862.  
16315222 R.L.Remmele, W.J.Callahan, S.Krishnan, L.Zhou, P.V.Bondarenko, A.C.Nichols, G.R.Kleemann, G.D.Pipes, S.Park, S.Fodor, E.Kras, and D.N.Brems (2006).
Active dimer of Epratuzumab provides insight into the complex nature of an antibody aggregate.
  J Pharm Sci, 95, 126-145.  
15856483 F.Rodier, R.P.Bahadur, P.Chakrabarti, and J.Janin (2005).
Hydration of protein-protein interfaces.
  Proteins, 60, 36-45.  
15858274 G.H.Cohen, E.W.Silverton, E.A.Padlan, F.Dyda, J.A.Wibbenmeyer, R.C.Willson, and D.R.Davies (2005).
Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry.
  Acta Crystallogr D Biol Crystallogr, 61, 628-633.
PDB code: 1yqv
15067677 N.Basdevant, D.Borgis, and T.Ha-Duong (2004).
A semi-implicit solvent model for the simulation of peptides and proteins.
  J Comput Chem, 25, 1015-1029.  
12444085 A.Yokota, K.Tsumoto, M.Shiroishi, H.Kondo, and I.Kumagai (2003).
The role of hydrogen bonding via interfacial water molecules in antigen-antibody complexation. The HyHEL-10-HEL interaction.
  J Biol Chem, 278, 5410-5418.
PDB codes: 1j1o 1j1p 1j1x
12657787 L.O.Essen, A.Harrenga, C.Ostermeier, and H.Michel (2003).
1.3 A X-ray structure of an antibody Fv fragment used for induced membrane-protein crystallization.
  Acta Crystallogr D Biol Crystallogr, 59, 677-687.
PDB code: 1mqk
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.  
11168890 K.Burgess, I.Han, A.Zhang, W.H.Zheng, K.Shanmugam, M.S.Featherstone, and H.U.Saragovi (2001).
DiSSiMiL: Diverse Small Size Mini-Libraries applied to simple and rapid epitope mapping of a monoclonal antibody.
  J Pept Res, 57, 68-76.  
11468348 P.V.Afonin, A.V.Fokin, I.N.Tsygannik, I.Y.Mikhailova, L.V.Onoprienko, I.I.Mikhaleva, V.T.Ivanov, T.Y.Mareeva, V.A.Nesmeyanov, N.Li, W.A.Pangborn, W.L.Duax, and V.Z.Pletnev (2001).
Crystal structure of an anti-interleukin-2 monoclonal antibody Fab complexed with an antigenic nonapeptide.
  Protein Sci, 10, 1514-1521.
PDB code: 1f90
10899782 D.Fleury, R.S.Daniels, J.J.Skehel, M.Knossow, and T.Bizebard (2000).
Structural evidence for recognition of a single epitope by two distinct antibodies.
  Proteins, 40, 572-578.
PDB code: 1eo8
11112523 E.J.Sundberg, M.Urrutia, B.C.Braden, J.Isern, D.Tsuchiya, B.A.Fields, E.L.Malchiodi, J.Tormo, F.P.Schwarz, and R.A.Mariuzza (2000).
Estimation of the hydrophobic effect in an antigen-antibody protein-protein interface.
  Biochemistry, 39, 15375-15387.
PDB codes: 1g7h 1g7i 1g7j 1g7l 1g7m
10828942 Y.Li, H.Li, S.J.Smith-Gill, and R.A.Mariuzza (2000).
Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,).
  Biochemistry, 39, 6296-6309.
PDB codes: 1dqj 1dqm 1dqq
10500196 J.J.Boniface, Z.Reich, D.S.Lyons, and M.M.Davis (1999).
Thermodynamics of T cell receptor binding to peptide-MHC: evidence for a general mechanism of molecular scanning.
  Proc Natl Acad Sci U S A, 96, 11446-11451.  
10440996 P.A.Ramsland, B.F.Movafagh, M.Reichlin, and A.B.Edmundson (1999).
Interference of rheumatoid factor activity by aspartame, a dipeptide methyl ester.
  J Mol Recognit, 12, 249-257.  
9700501 B.C.Braden, E.R.Goldman, R.A.Mariuzza, and R.J.Poljak (1998).
Anatomy of an antibody molecule: structure, kinetics, thermodynamics and mutational studies of the antilysozyme antibody D1.3.
  Immunol Rev, 163, 45-57.  
9461077 D.Fleury, S.A.Wharton, J.J.Skehel, M.Knossow, and T.Bizebard (1998).
Antigen distortion allows influenza virus to escape neutralization.
  Nat Struct Biol, 5, 119-123.
PDB codes: 2vir 2vis 2vit 2viu
9649307 W.Dall'Acqua, A.L.Simon, M.G.Mulkerrin, and P.Carter (1998).
Contribution of domain interface residues to the stability of antibody CH3 domain homodimers.
  Biochemistry, 37, 9266-9273.  
9609690 W.Dall'Acqua, E.R.Goldman, W.Lin, C.Teng, D.Tsuchiya, H.Li, X.Ysern, B.C.Braden, Y.Li, S.J.Smith-Gill, and R.A.Mariuzza (1998).
A mutational analysis of binding interactions in an antigen-antibody protein-protein complex.
  Biochemistry, 37, 7981-7991.
PDB code: 1a2y
9434905 I.A.Wilson, and K.C.Garcia (1997).
T-cell receptor structure and TCR complexes.
  Curr Opin Struct Biol, 7, 839-848.  
9336207 K.A.Xavier, K.A.Shick, S.J.Smith-Gil, and R.C.Willson (1997).
Involvement of water molecules in the association of monoclonal antibody HyHEL-5 with bobwhite quail lysozyme.
  Biophys J, 73, 2116-2125.  
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.