PDBsum entry 2fl5

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protein ligands Protein-protein interface(s) links
Immune system PDB id
Jmol PyMol
Protein chains
209 a.a. *
220 a.a. *
RBF ×4
Waters ×144
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Cofactor-containing antibodies: crystal structure of the ori yellow antibody
Structure: Immunoglobulin igg1 lambda light chain. Chain: l, a, c, e. Immunoglobulin igg1 heavy chain. Chain: h, b, d, f
Source: Homo sapiens. Human. Organism_taxid: 9606. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
3.00Å     R-factor:   0.240     R-free:   0.290
Authors: X.Zhu,I.A.Wilson
Key ref:
X.Zhu et al. (2006). Cofactor-containing antibodies: crystal structure of the original yellow antibody. Proc Natl Acad Sci U S A, 103, 3581-3585. PubMed id: 16537445 DOI: 10.1073/pnas.0600251103
05-Jan-06     Release date:   21-Feb-06    
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Protein chains
Pfam   ArchSchema ?
Q5FWF9  (Q5FWF9_HUMAN) -  IGL@ protein
232 a.a.
209 a.a.*
Protein chains
No UniProt id for this chain
Struc: 220 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 19 residue positions (black crosses)


DOI no: 10.1073/pnas.0600251103 Proc Natl Acad Sci U S A 103:3581-3585 (2006)
PubMed id: 16537445  
Cofactor-containing antibodies: crystal structure of the original yellow antibody.
X.Zhu, P.Wentworth, R.A.Kyle, R.A.Lerner, I.A.Wilson.
Antibodies are generally thought to be a class of proteins that function without the use of cofactors. However, it is not widely appreciated that antibodies are believed to be the major carrier protein in human circulation for the important riboflavin cofactor that is involved in a host of biological phenomena. A further link between riboflavin and antibodies was discovered 30 years ago when a bright-yellow antibody, IgG(GAR), was purified from a patient with multiple myeloma who had turned yellow during the course of her disease. It was subsequently shown that the yellow color of this antibody was due to riboflavin binding. However, it was not known how and where riboflavin was bound to this antibody. We now report the crystal structure of this historically important IgG(GAR) Fab at 3.0-A resolution. The riboflavin is located in the antigen-combining site with its isoalloxazine ring stacked between the parallel aromatic moieties of TyrH33, PheH58, and TyrH100A. Together with additional hydrogen bonds, these interactions reveal the structural basis for high-affinity riboflavin binding. The ligand specificity of IgG(GAR) is compared with another riboflavin-binding antibody, IgG(DOT), which was purified from a second patient with multiple myeloma. The crystal structure of IgG(GAR) provides a starting point for attempts to understand the physiological relevance and chemical functions of cofactor-containing antibodies.
  Selected figure(s)  
Figure 1.
Fig. 1. Chemical structures of riboflavin, FMN, FAD, and six riboflavin analogues: roseoflavin, 8-propylamino riboflavin, lumazine, 3-methyl riboflavin, 3-carboxymethyl riboflavin, and 3-(N-methylamidomethyl) riboflavin.
Figure 4.
Fig. 4. Schematic presentation of riboflavin binding site in IgG^GAR. Residues forming van der Waals’ interactions with the riboflavin are indicated by an arc with radiating spokes toward the ligand atoms they contact; those participating in the hydrogen bonds with the riboflavin are shown in ball-and-stick representations. Hydrogen bonds are illustrated as blue dotted lines. Carbon atoms are colored in black, nitrogen atoms in blue, and oxygen atoms in red. Atom names of the riboflavin are labeled. The figure was generated from the program LIGPLOT (29).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21298133 R.A.Lerner (2011).
Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire.
  Mol Biosyst, 7, 1004-1012.  
  20944764 R.A.Kyle, and W.C.Roberts (2010).
Robert Arthur Kyle, MD: a conversation with the editor.
  Proc (Bayl Univ Med Cent), 23, 400-418.  
17828757 H.Liu, G.Gaza-Bulseco, D.Faldu, C.Chumsae, and J.Sun (2008).
Heterogeneity of monoclonal antibodies.
  J Pharm Sci, 97, 2426-2447.  
17360412 Y.Xu, M.S.Hixon, N.Yamamoto, L.A.McAllister, A.D.Wentworth, P.Wentworth, and K.D.Janda (2007).
Antibody-catalyzed anaerobic destruction of methamphetamine.
  Proc Natl Acad Sci U S A, 104, 3681-3686.  
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.