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PDBsum entry 1c08

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protein Protein-protein interface(s) links
Immune system/hydrolase PDB id
1c08
Jmol
Contents
Protein chains
107 a.a. *
114 a.a. *
129 a.a. *
Waters ×125
* Residue conservation analysis
PDB id:
1c08
Name: Immune system/hydrolase
Title: Crystal structure of hyhel-10 fv-hen lysozyme complex
Structure: Anti-hen egg white lysozyme antibody (hyhel-10). Chain: a. Fragment: vl fragment. Engineered: yes. Anti-hen egg white lysozyme antibody (hyhel-10). Chain: b. Fragment: vh fragment. Engineered: yes. Lysozyme.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031
Biol. unit: Trimer (from PQS)
Resolution:
2.30Å     R-factor:   0.235     R-free:   0.175
Authors: M.Shiroishi,H.Kondo,M.Matsushima,K.Tsumoto,I.Kumagai
Key ref:
H.Kondo et al. (1999). Crystal structure of anti-Hen egg white lysozyme antibody (HyHEL-10) Fv-antigen complex. Local structural changes in the protein antigen and water-mediated interactions of Fv-antigen and light chain-heavy chain interfaces. J Biol Chem, 274, 27623-27631. PubMed id: 10488102 DOI: 10.1074/jbc.274.39.27623
Date:
15-Jul-99     Release date:   19-Jul-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 107 a.a.
Protein chain
Pfam   ArchSchema ?
P01823  (HVM47_MOUSE) -  Ig heavy chain V region 36-60
Seq:
Struc:
113 a.a.
114 a.a.*
Protein chain
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
Seq:
Struc:
147 a.a.
129 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain C: E.C.3.2.1.17  - 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   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     7 terms  

 

 
DOI no: 10.1074/jbc.274.39.27623 J Biol Chem 274:27623-27631 (1999)
PubMed id: 10488102  
 
 
Crystal structure of anti-Hen egg white lysozyme antibody (HyHEL-10) Fv-antigen complex. Local structural changes in the protein antigen and water-mediated interactions of Fv-antigen and light chain-heavy chain interfaces.
H.Kondo, M.Shiroishi, M.Matsushima, K.Tsumoto, I.Kumagai.
 
  ABSTRACT  
 
In order to address the recognition mechanism of the fragments of antibody variable regions, termed Fv, toward their target antigen, an x-ray crystal structure of an anti-hen egg white lysozyme antibody (HyHEL-10) Fv fragment complexed with its cognate antigen, hen egg white lysozyme (HEL), was solved at 2.3 A. The overall structure of the complex is similar to that reported in a previous article dealing with the Fab fragment-HEL complex (PDB ID code,). However, the areas of Fv covered by HEL upon complex formation increased by about 100 A(2) in comparison with the Fab-HEL complex, and two local structural differences were observed in the heavy chain of the variable region (VH). In addition, small but significant local structural changes were observed in the antigen, HEL. The x-ray data permitted the identification of two water molecules between the VH and HEL and six water molecules retained in the interface between the antigen and the light chain complementarity determining regions (CDRs) 2 and 3 (CDR-L2 and CDR-L3). These water molecules bridge the antigen-antibody interface through hydrogen bond formation in the VL-HEL interface. Eleven water molecules were found to complete the imperfect VH-VL interface, suggesting that solvent molecules mediate the stabilization of interaction between variable regions. These results suggest that the unfavorable effect of deletion of constant regions on the antigen-antibody interaction is compensated by an increase in favorable interactions, including structural changes in the antigen-antibody interface and solvent-mediated hydrogen bond formation upon complex formation, which may lead to a minimum decreased affinity of the antibody Fv fragment toward its antigen.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Schematic model of HyHEL-10 Fv-HEL complex. The Fv-HEL complex model, of which the C coordinates of HEL are superimposed on the C coordinates of HEL complexed with Fab, is superimposed on the Fab model (gray). This model was produced with the programs MOLSCRIPT (69) and Raster3D (70). VH, cyan; VL, green; HEL, magenta.
Figure 6.
Fig. 6. Comparison of side chains and main chains in Fv with those in Fab. Fab is represented with light gray sticks and Fv by dark gray sticks. A, CDR-H1 loop. B, CDR-H3 loop. The water molecule of Fab exists near HAsp-96 of Fv. The C backbone of VL is represented with a thick stick. The figure was generated using WebLab Viewer (MSI).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 27623-27631) copyright 1999.  
  Figures were selected by an automated process.  

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
20412054 M.Umetsu, T.Nakanishi, R.Asano, T.Hattori, and I.Kumagai (2010).
Protein-protein interactions and selection: generation of molecule-binding proteins on the basis of tertiary structural information.
  FEBS J, 277, 2006-2014.  
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.  
18227432 T.Nakanishi, K.Tsumoto, A.Yokota, H.Kondo, and I.Kumagai (2008).
Critical contribution of VH-VL interaction to reshaping of an antibody: the case of humanization of anti-lysozyme antibody, HyHEL-10.
  Protein Sci, 17, 261-270.
PDB codes: 2eiz 2eks 2yss
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.  
18441234 Y.Urakubo, T.Ikura, and N.Ito (2008).
Crystal structural analysis of protein-protein interactions drastically destabilized by a single mutation.
  Protein Sci, 17, 1055-1065.
PDB code: 2za4
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.  
16649995 K.Masuda, K.Sakamoto, M.Kojima, T.Aburatani, T.Ueda, and H.Ueda (2006).
The role of interface framework residues in determining antibody V(H)/V(L) interaction strength and antigen-binding affinity.
  FEBS J, 273, 2184-2194.  
17145365 R.J.Duquesnoy (2006).
A structurally based approach to determine HLA compatibility at the humoral immune level.
  Hum Immunol, 67, 847-862.  
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
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
14500870 M.Adachi, Y.Kurihara, H.Nojima, M.Takeda-Shitaka, K.Kamiya, and H.Umeyama (2003).
Interaction between the antigen and antibody is controlled by the constant domains: normal mode dynamics of the HEL-HyHEL-10 complex.
  Protein Sci, 12, 2125-2131.  
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
11813165 E.B.Plüger, M.Boes, C.Alfonso, C.J.Schröter, H.Kalbacher, H.L.Ploegh, and C.Driessen (2002).
Specific role for cathepsin S in the generation of antigenic peptides in vivo.
  Eur J Immunol, 32, 467-476.  
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
12237453 J.Pons, J.R.Stratton, and J.F.Kirsch (2002).
How do two unrelated antibodies, HyHEL-10 and F9.13.7, recognize the same epitope of hen egg-white lysozyme?
  Protein Sci, 11, 2308-2315.  
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.  
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.  
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.