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PDBsum entry 1zv5

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Hydrolase/immune system PDB id
1zv5
Jmol
Contents
Protein chains
129 a.a. *
119 a.a. *
Ligands
PO4 ×2
Waters ×46
* Residue conservation analysis
PDB id:
1zv5
Name: Hydrolase/immune system
Title: Crystal structure of the variable domain of the camelid heavy-chain antibody d2-l29 in complex with hen egg white lysozyme
Structure: LysozymE C. Chain: l. Synonym: 1,4-beta-n-acetylmuramidasE C, allergen gal d 4, gal d iv. Immunoglobulin heavy chain antibody variable domain. Chain: a. Fragment: vhh d2-l29. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Camelus dromedarius. Arabian camel. Organism_taxid: 9838. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.217     R-free:   0.239
Authors: E.De Genst,K.Silence,K.Decanniere,K.Conrath,R.Loris,J.Kinne, S.Muyldermans,L.Wyns
Key ref:
E.De Genst et al. (2006). Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proc Natl Acad Sci U S A, 103, 4586-4591. PubMed id: 16537393 DOI: 10.1073/pnas.0505379103
Date:
01-Jun-05     Release date:   04-Apr-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
Seq:
Struc:
147 a.a.
129 a.a.
Protein chain
No UniProt id for this chain
Struc: 119 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain L: 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   3 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
DOI no: 10.1073/pnas.0505379103 Proc Natl Acad Sci U S A 103:4586-4591 (2006)
PubMed id: 16537393  
 
 
Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies.
E.De Genst, K.Silence, K.Decanniere, K.Conrath, R.Loris, J.Kinne, S.Muyldermans, L.Wyns.
 
  ABSTRACT  
 
Clefts on protein surfaces are avoided by antigen-combining sites of conventional antibodies, in contrast to heavy-chain antibodies (HCAbs) of camelids that seem to be attracted by enzymes' substrate pockets. The explanation for this pronounced preference of HCAbs was investigated. Eight single domain antigen-binding fragments of HCAbs (VHH) with nanomolar affinities for lysozyme were isolated from three immunized dromedaries. Six of eight VHHs compete with small lysozyme inhibitors. This ratio of active site binders is also found within the VHH pool derived from polyclonal HCAbs purified from the serum of the immunized dromedary. The crystal structures of six VHHs in complex with lysozyme and their interaction surfaces were compared to those of conventional antibodies with the same antigen. The interface sizes of VHH and conventional antibodies to lysozyme are very similar as well as the number and chemical nature of the contacts. The main difference comes from the compact prolate shape of VHH that presents a large convex paratope, predominantly formed by the H3 loop and interacting, although with different structures, into the concave lysozyme substrate-binding pocket. Therefore, a single domain antigen-combining site has a clear structural advantage over a conventional dimeric format for targeting clefts on antigenic surfaces.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Epitope mapping of the monoclonal and polyclonal VHHs. (A) HEWL binding of all VHHs in the presence of a saturating concentration of cAb-Lys-3 using a coinjection procedure. (B) Epitopes of HEWL active site binders based on the inhibition of binding by NAG3 and Biebrich Scarlet. (C) Residual HEWL binding of polyclonal VHH derived from the IgG3 fraction of dromedary D2. (Left) Binding in absence of competitor (set at 100%). (Center) Binding in presence of HEWL-saturating concentrations of D2-L24. (Right) Binding in presence of HEWL-saturating concentrations of D2-L19.
Figure 3.
Fig. 3. Superposition of the antibody-lysozyme complexes for conventional antibodies (Left) and for VHHs (Right). The HEWL molecules (gray surfaces) are shown in the same orientation for both antibody classes. The antibody molecules are represented as colored ribbons and their identity is indicated in the same color.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21244216 F.Rahbarizadeh, D.Ahmadvand, and Z.Sharifzadeh (2011).
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PDB code: 3k3q
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PDB codes: 3m18 3m19
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  J Virol, 82, 9753-9764.  
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PDB codes: 3csb 3csg
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  J Mol Biol, 373, 941-953.
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Heating as a rapid purification method for recovering correctly-folded thermotolerant VH and VHH domains.
  BMC Biotechnol, 7, 7.  
18042730 G.Habicht, C.Haupt, R.P.Friedrich, P.Hortschansky, C.Sachse, J.Meinhardt, K.Wieligmann, G.P.Gellermann, M.Brodhun, J.Götz, K.J.Halbhuber, C.Röcken, U.Horn, and M.Fändrich (2007).
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  Proc Natl Acad Sci U S A, 104, 19232-19237.  
17195019 M.J.Taussig, O.Stoevesandt, C.A.Borrebaeck, A.R.Bradbury, D.Cahill, C.Cambillau, A.de Daruvar, S.Dübel, J.Eichler, R.Frank, T.J.Gibson, D.Gloriam, L.Gold, F.W.Herberg, H.Hermjakob, J.D.Hoheisel, T.O.Joos, O.Kallioniemi, M.Koegl, M.Koegll, Z.Konthur, B.Korn, E.Kremmer, S.Krobitsch, U.Landegren, S.van der Maarel, J.McCafferty, S.Muyldermans, P.A.Nygren, S.Palcy, A.Plückthun, B.Polic, M.Przybylski, P.Saviranta, A.Sawyer, D.J.Sherman, A.Skerra, M.Templin, M.Ueffing, and M.Uhlén (2007).
ProteomeBinders: planning a European resource of affinity reagents for analysis of the human proteome.
  Nat Methods, 4, 13-17.  
17512622 M.Jain, N.Kamal, and S.K.Batra (2007).
Engineering antibodies for clinical applications.
  Trends Biotechnol, 25, 307-316.  
17704915 M.M.Harmsen, and H.J.De Haard (2007).
Properties, production, and applications of camelid single-domain antibody fragments.
  Appl Microbiol Biotechnol, 77, 13-22.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17291278 Y.H.Chien, and Y.Konigshofer (2007).
Antigen recognition by gammadelta T cells.
  Immunol Rev, 215, 46-58.  
18077410 Y.Wu, C.Eigenbrot, W.C.Liang, S.Stawicki, S.Shia, B.Fan, R.Ganesan, M.T.Lipari, and D.Kirchhofer (2007).
Structural insight into distinct mechanisms of protease inhibition by antibodies.
  Proc Natl Acad Sci U S A, 104, 19784-19789.
PDB codes: 2r0k 2r0l
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.