PDBsum entry 2bfv

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Immunoglobulin PDB id
Protein chains
112 a.a. *
119 a.a. *
Waters ×55
* Residue conservation analysis
PDB id:
Name: Immunoglobulin
Title: Monoclonal antibody fragment fv4155 from e. Coli
Structure: Fv4155. Chain: l. Fragment: monoclonal antibody fv fragment. Engineered: yes. Fv4155. Chain: h. Fragment: monoclonal antibody fv fragment. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.187    
Authors: C.H.Trinh,S.E.V.Phillips
Key ref:
C.H.Trinh et al. (1997). Antibody fragment Fv4155 bound to two closely related steroid hormones: the structural basis of fine specificity. Structure, 5, 937-948. PubMed id: 9261086 DOI: 10.1016/S0969-2126(97)00247-5
27-May-97     Release date:   03-Dec-97    
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Protein chain
Pfam   ArchSchema ?
P01631  (KV2A7_MOUSE) -  Ig kappa chain V-II region 26-10
113 a.a.
112 a.a.*
Protein chain
No UniProt id for this chain
Struc: 119 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 20 residue positions (black crosses)


DOI no: 10.1016/S0969-2126(97)00247-5 Structure 5:937-948 (1997)
PubMed id: 9261086  
Antibody fragment Fv4155 bound to two closely related steroid hormones: the structural basis of fine specificity.
C.H.Trinh, S.D.Hemmington, M.E.Verhoeyen, S.E.Phillips.
BACKGROUND: The concentration of steroid glucuronides in serial samples of early morning urine (EMU) can be used to predict the fertile period in the female menstrual cycle. The monoclonal antibody 4155 has been used as a convenient means of measuring the concentration of steroid glucuronides in EMU, as it specifically recognises the steroid hormone estrone beta-D-glucuronide (E3G), with very high affinity, and the closely related hormone estriol 3-(beta-d-glucuronide) (EI3G), with reduced affinity. Although 4115 binds these hormones with different affinities, EI3G differs from E3G only in the addition of a hydroxyl group and reduction of an adjacent carbonyl. To investigate the structural basis of this fine binding specificity, we have determined the crystal structures of the variable fragment (Fv) of 4155 in complex with each of these hormones. RESULTS: Two crystal forms of the Fv4155-EI3G complex, at resolutions of 2.1 A and 2.5 A, and one form of the Fv4155-E3G complex, at 2.1 A resolution were solved and refined. The crystal structures show the E3G or EI3G antigen lying in an extended cleft, running form the centre of the antibody combining site down one side of the variable domain interface, and formed almost entirely from residues in the heavy chain. The binding cleft lies primarily between the heavy chain complementarity determining regions (CDRs), rather than in the interface between the heavy and light chains. In both complexes the binding of the glucuronic sugar, and rings A and B of the steroid, is specified by the shape of the narrow cleft. Analysis of the Fv structure reveals that five of the six CDR regions can be assigned to one of the predefined canonical structural classes. CONCLUSIONS: The difference in the binding affinity of Fv4155 for the two steroid hormones is accounted for by a subtle combination of a less favoured hydrogen-bond geometry, and a minor rearrangement of the water molecule network around the binding site. The rearrangement of water molecules results from the burial of the additional hydroxyl group of the EI3G in a hydrophobic environment.
  Selected figure(s)  
Figure 2.
Figure 2. The overall fold of the Fv fragment, Fv4155. (a) Stereoview of the Ca tracing of Fv4155. The N and C termini and every tenth residue are labelled for both the light (L; purple) and heavy (H; green) chains; Ca positions are marked by black spheres. (b) A ribbon diagram of the Fv fragment Fv4155 in the same orientation as (a). The V[L] and V[H] chains are coloured purple and green, respectively. The bound E3G molecule is shown in white ball-and-stick representation. (Figures were generated using the programs MOLSCRIPT [51] and Raster 3D [52].)
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 937-948) copyright 1997.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360611 M.H.Niemi, K.Takkinen, L.K.Amundsen, H.Söderlund, J.Rouvinen, and M.Höyhtyä (2011).
The testosterone binding mechanism of an antibody derived from a naïve human scFv library.
  J Mol Recognit, 24, 209-219.
PDB code: 3kdm
21161086 M.Ui, Y.Tanaka, T.Tsumuraya, I.Fujii, M.Inoue, M.Hirama, and K.Tsumoto (2011).
Structural and energetic hot-spots for the interaction between a ladder-like polycyclic ether and the anti-ciguatoxin antibody 10C9Fab.
  Mol Biosyst, 7, 793-798.  
17712773 P.Scheerer, A.Kramer, L.Otte, M.Seifert, H.Wessner, C.Scholz, N.Krauss, J.Schneider-Mergener, and W.Höhne (2007).
Structure of an anti-cholera toxin antibody Fab in complex with an epitope-derived D-peptide: a case of polyspecific recognition.
  J Mol Recognit, 20, 263-274.
PDB code: 1zea
16782791 P.J.Kundrotas, and E.Alexov (2006).
Electrostatic properties of protein-protein complexes.
  Biophys J, 91, 1724-1736.  
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
12709438 I.Kumagai, Y.Nishimiya, H.Kondo, and K.Tsumoto (2003).
Structural consequences of target epitope-directed functional alteration of an antibody. The case of anti-hen lysozyme antibody, HyHEL-10.
  J Biol Chem, 278, 24929-24936.
PDB codes: 1ua6 1uac
14500876 L.C.James, and D.S.Tawfik (2003).
The specificity of cross-reactivity: promiscuous antibody binding involves specific hydrogen bonds rather than nonspecific hydrophobic stickiness.
  Protein Sci, 12, 2183-2193.  
12610298 L.C.James, P.Roversi, and D.S.Tawfik (2003).
Antibody multispecificity mediated by conformational diversity.
  Science, 299, 1362-1367.
PDB codes: 1oaq 1oar 1oau 1oax 1oay 1oaz 1ocw
12196551 J.Valjakka, A.Hemminki, S.Niemi, H.Söderlund, K.Takkinen, and J.Rouvinen (2002).
Crystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domains.
  J Biol Chem, 277, 44021-44027.
PDB codes: 1l7s 1l7t 1vpo
11707437 J.Valjakka, K.Takkinenz, T.Teerinen, H.Söderlund, and J.Rouvinen (2002).
Structural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound forms.
  J Biol Chem, 277, 4183-4190.
PDB codes: 1i9i 1i9j
11870917 S.Coulon, J.L.Pellequer, T.Blachère, M.Chartier, E.Mappus, S.W.Chen Sw, C.Y.Cuilleron, and D.Baty (2002).
Functional characterization of an anti-estradiol antibody by site-directed mutagenesis and molecular modelling: modulation of binding properties and prominent role of the V(L) domain in estradiol recognition.
  J Mol Recognit, 15, 6.  
11301480 F.Bettsworth, C.Monnet, B.Watelet, N.Battail-Poirot, B.Gilquin, M.Jolivet, A.Menez, M.Arnaud, and F.Ducancel (2001).
Functional characterization of two anti-estradiol antibodies as deduced from modelling and site-directed mutagenesis experiments.
  J Mol Recognit, 14, 99.  
10684599 S.Spinelli, L.G.Frenken, P.Hermans, T.Verrips, K.Brown, M.Tegoni, and C.Cambillau (2000).
Camelid heavy-chain variable domains provide efficient combining sites to haptens.
  Biochemistry, 39, 1217-1222.
PDB code: 1qd0
11092942 U.Lamminmäki, and J.Kankare (2000).
Crystallization and preliminary X-ray analysis of a recombinant Fab fragment in complex with 17beta-oestradiol.
  Acta Crystallogr D Biol Crystallogr, 56, 1670-1672.  
9729735 W.Dall'Acqua, and P.Carter (1998).
Antibody engineering.
  Curr Opin Struct Biol, 8, 443-450.  
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.