PDBsum entry 1dqm

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protein Protein-protein interface(s) links
Immune system PDB id
Protein chains
214 a.a. *
209 a.a. *
Waters ×336
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Crystal structure of anti-lysozyme antibody
Structure: Anti-lysozyme antibody hyhel-63 (light chain). Chain: l. Fragment: fab fragment. Engineered: yes. Anti-lysozyme antibody hyhel-63 (heavy chain). Chain: h. Fragment: fab fragment. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.10Å     R-factor:   0.225     R-free:   0.268
Authors: H.Li,R.A.Mariuzza
Key ref:
Y.Li et al. (2000). Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,). Biochemistry, 39, 6296-6309. PubMed id: 10828942 DOI: 10.1021/bi000054l
04-Jan-00     Release date:   19-Jan-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01837  (IGKC_MOUSE) -  Ig kappa chain C region
106 a.a.
214 a.a.
Protein chain
No UniProt id for this chain
Struc: 209 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   1 term 
  Biochemical function     antigen binding     1 term  


DOI no: 10.1021/bi000054l Biochemistry 39:6296-6309 (2000)
PubMed id: 10828942  
Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,).
Y.Li, H.Li, S.J.Smith-Gill, R.A.Mariuzza.
Antigen-antibody complexes provide useful models for studying the structure and energetics of protein-protein interactions. We report the cloning, bacterial expression, and crystallization of the antigen-binding fragment (Fab) of the anti-hen egg white lysozyme (HEL) antibody HyHEL-63 in both free and antigen-bound forms. The three-dimensional structure of Fab HyHEL-63 complexed with HEL was determined to 2.0 A resolution, while the structure of the unbound antibody was determined in two crystal forms, to 1.8 and 2.1 A resolution. In the complex, 19 HyHEL-63 residues from all six complementarity-determining regions (CDRs) of the antibody contact 21 HEL residues from three discontinuous polypeptide segments of the antigen. The interface also includes 11 bound water molecules, 3 of which are completely buried in the complex. Comparison of the structures of free and bound Fab HyHEL-63 reveals that several of the ordered water molecules in the free antibody-combining site are retained and that additional waters are added upon complex formation. The interface waters serve to increase shape and chemical complementarity by filling cavities between the interacting surfaces and by contributing to the hydrogen bonding network linking the antigen and antibody. Complementarity is further enhanced by small (<3 A) movements in the polypeptide backbones of certain antibody CDR loops, by rearrangements of side chains in the interface, and by a slight shift in the relative orientation of the V(L) and V(H) domains. The combining site residues of complexed Fab HyHEL-63 exhibit reduced temperature factors compared with those of the free Fab, suggesting a loss in conformational entropy upon binding. To probe the relative contribution of individual antigen residues to complex stabilization, single alanine substitutions were introduced in the epitope of HEL recognized by HyHEL-63, and their effects on antibody affinity were measured using surface plasmon resonance. In agreement with the crystal structure, HEL residues at the center of the interface that are buried in the complex contribute most to the binding energetics (DeltaG(mutant) - DeltaG(wild type) > 3.0 kcal/mol), whereas the apparent contributions of solvent-accessible residues at the periphery are much less pronounced (<1.5 kcal/mol). In the latter case, the mutations may be partially compensated by local rearrangements in solvent structure that help preserve shape complementarity and the interface hydrogen bonding network.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20544968 D.J.Diller, C.Humblet, X.Zhang, and L.M.Westerhoff (2010).
Computational alanine scanning with linear scaling semiempirical quantum mechanical methods.
  Proteins, 78, 2329-2337.  
19089973 N.Wang, W.F.Smith, B.R.Miller, D.Aivazian, A.A.Lugovskoy, M.E.Reff, S.M.Glaser, L.J.Croner, and S.J.Demarest (2009).
Conserved amino acid networks involved in antibody variable domain interactions.
  Proteins, 76, 99.  
18295796 D.M.Zajonc, P.B.Savage, A.Bendelac, I.A.Wilson, and L.Teyton (2008).
Crystal structures of mouse CD1d-iGb3 complex and its cognate Valpha14 T cell receptor suggest a model for dual recognition of foreign and self glycolipids.
  J Mol Biol, 377, 1104-1116.
PDB codes: 2q7y 2q86
18383102 K.Kourentzi, M.Srinivasan, S.J.Smith-Gill, and R.C.Willson (2008).
Conformational flexibility and kinetic complexity in antibody-antigen interactions.
  J Mol Recognit, 21, 114-121.  
18184701 Q.Wang, F.Cheng, M.Lu, X.Tian, and J.Ma (2008).
Crystal structure of unliganded influenza B virus hemagglutinin.
  J Virol, 82, 3011-3020.
PDB code: 3bt6
18234071 V.Moreau, C.Fleury, D.Piquer, C.Nguyen, N.Novali, S.Villard, D.Laune, C.Granier, and F.Molina (2008).
PEPOP: computational design of immunogenic peptides.
  BMC Bioinformatics, 9, 71.  
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
17652781 N.Sinha, Y.Li, C.A.Lipschultz, and S.J.Smith-Gill (2007).
Understanding antibody-antigen associations by molecular dynamics simulations: detection of important intra- and inter-molecular salt bridges.
  Cell Biochem Biophys, 47, 361-375.  
16487065 P.Gupta, M.Saleemuddin, and R.H.Khan (2006).
Hydrophobic interactions are the prevalent force in bromelain:Fab' complex.
  Biochemistry (Mosc), 71, S31-S37.  
17145365 R.J.Duquesnoy (2006).
A structurally based approach to determine HLA compatibility at the humoral immune level.
  Hum Immunol, 67, 847-862.  
15778956 D.Segal, and M.Eisenstein (2005).
The effect of resolution-dependent global shape modifications on rigid-body protein-protein docking.
  Proteins, 59, 580-591.  
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
15713683 M.Becker, J.Bunikis, B.D.Lade, J.J.Dunn, A.G.Barbour, and C.L.Lawson (2005).
Structural investigation of Borrelia burgdorferi OspB, a bactericidal Fab target.
  J Biol Chem, 280, 17363-17370.
PDB codes: 1p4p 1rjl
15698573 Y.Li, Y.Huang, C.P.Swaminathan, S.J.Smith-Gill, and R.A.Mariuzza (2005).
Magnitude of the hydrophobic effect at central versus peripheral sites in protein-protein interfaces.
  Structure, 13, 297-307.
PDB codes: 1xgp 1xgq 1xgr 1xgt 1xgu
15162493 A.Berchanski, B.Shapira, and M.Eisenstein (2004).
Hydrophobic complementarity in protein-protein docking.
  Proteins, 56, 130-142.  
14988501 A.Cauerhff, F.A.Goldbaum, and B.C.Braden (2004).
Structural mechanism for affinity maturation of an anti-lysozyme antibody.
  Proc Natl Acad Sci U S A, 101, 3539-3544.
PDB code: 1p2c
15606760 E.Graciet, G.Mulliert, S.Lebreton, and B.Gontero (2004).
Involvement of two positively charged residues of Chlamydomonas reinhardtii glyceraldehyde-3-phosphate dehydrogenase in the assembly process of a bi-enzyme complex involved in CO2 assimilation.
  Eur J Biochem, 271, 4737-4744.  
15564505 W.D.Crill, and G.J.Chang (2004).
Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes.
  J Virol, 78, 13975-13986.  
14962388 Y.Zhao, Z.Li, S.J.Drozd, Y.Guo, W.Mourad, and H.Li (2004).
Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex.
  Structure, 12, 277-288.
PDB code: 1r5i
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
12784371 R.Chen, L.Li, and Z.Weng (2003).
ZDOCK: an initial-stage protein-docking algorithm.
  Proteins, 52, 80-87.  
14581222 S.Mohan, N.Sinha, and S.J.Smith-Gill (2003).
Modeling the binding sites of anti-hen egg white lysozyme antibodies HyHEL-8 and HyHEL-26: an insight into the molecular basis of antibody cross-reactivity and specificity.
  Biophys J, 85, 3221-3236.  
12740607 Y.Li, H.Li, F.Yang, S.J.Smith-Gill, and R.A.Mariuzza (2003).
X-ray snapshots of the maturation of an antibody response to a protein antigen.
  Nat Struct Biol, 10, 482-488.
PDB codes: 1ndg 1ndm
12501160 A.V.Veselovsky, Y.D.Ivanov, A.S.Ivanov, A.I.Archakov, P.Lewi, and P.Janssen (2002).
Protein-protein interactions: mechanisms and modification by drugs.
  J Mol Recognit, 15, 405-422.  
11901152 E.Richard, S.M.Alam, F.X.Arredondo-Vega, D.D.Patel, and M.S.Hershfield (2002).
Clustered charged amino acids of human adenosine deaminase comprise a functional epitope for binding the adenosine deaminase complexing protein CD26/dipeptidyl peptidase IV.
  J Biol Chem, 277, 19720-19726.  
11994422 J.G.Luz, M.Huang, K.C.Garcia, M.G.Rudolph, V.Apostolopoulos, L.Teyton, and I.A.Wilson (2002).
Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: a buried alloreactive mutation subtly alters peptide presentation substantially increasing V(beta) Interactions.
  J Exp Med, 195, 1175-1186.
PDB codes: 1jtr 1leg 1lek 1mwa
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.  
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
11746948 R.L.Rich, and D.G.Myszka (2001).
Survey of the year 2000 commercial optical biosensor literature.
  J Mol Recognit, 14, 273-294.  
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.  
10903952 E.J.Sundberg, and R.A.Mariuzza (2000).
Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions.
  Structure, 8, R137-R142.  
11067872 E.Richard, F.X.Arredondo-Vega, I.Santisteban, S.J.Kelly, D.D.Patel, and M.S.Hershfield (2000).
The binding site of human adenosine deaminase for CD26/Dipeptidyl peptidase IV: the Arg142Gln mutation impairs binding to cd26 but does not cause immune deficiency.
  J Exp Med, 192, 1223-1236.  
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.