PDBsum entry 3l9j

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protein metals Protein-protein interface(s) links
Immune system PDB id
Protein chains
130 a.a. *
149 a.a. *
Waters ×246
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Selection of a novel highly specific tnfalpha antagonist: in the crystal structure of the antagonist-tnfalpha complex
Structure: Tnfalpha. Chain: c. Engineered: yes. Tumor necrosis factor, soluble form. Chain: t. Fragment: unp residues 85-233. Synonym: tnf-alpha, tumor necrosis factor ligand superfamil 2, tnf-a, cachectin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.175     R-free:   0.217
Authors: P.Byla,M.H.Andersen,H.C.Thogersen,H.H.Gad,R.Hartmann
Key ref: P.Byla et al. (2010). Selection of a novel and highly specific tumor necrosis factor alpha (TNFalpha) antagonist: insight from the crystal structure of the antagonist-TNFalpha complex. J Biol Chem, 285, 12096-12100. PubMed id: 20179326 DOI: 10.1074/jbc.M109.063305
05-Jan-10     Release date:   23-Feb-10    
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Protein chain
Pfam   ArchSchema ?
P05452  (TETN_HUMAN) -  Tetranectin
202 a.a.
130 a.a.*
Protein chain
Pfam   ArchSchema ?
P01375  (TNFA_HUMAN) -  Tumor necrosis factor
233 a.a.
149 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 18 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     immune response   1 term 
  Biochemical function     carbohydrate binding     2 terms  


DOI no: 10.1074/jbc.M109.063305 J Biol Chem 285:12096-12100 (2010)
PubMed id: 20179326  
Selection of a novel and highly specific tumor necrosis factor alpha (TNFalpha) antagonist: insight from the crystal structure of the antagonist-TNFalpha complex.
P.Byla, M.H.Andersen, T.L.Holtet, H.Jacobsen, M.Munch, H.H.Gad, H.C.Thøgersen, R.Hartmann.
Inhibition of tumor necrosis factor alpha (TNFalpha) is a favorable way of treating several important diseases such as rheumatoid arthritis, Crohn disease, and psoriasis. Therefore, an extensive range of TNFalpha inhibitory proteins, most of them based upon an antibody scaffold, has been developed and used with variable success as therapeutics. We have developed a novel technology platform using C-type lectins as a vehicle for the creation of novel trimeric therapeutic proteins with increased avidity and unique properties as compared with current protein therapeutics. We chose human TNFalpha as a test target to validate this new technology because of the extensive experience available with protein-based TNFalpha antagonists. Here, we present a novel and highly specific TNFalpha antagonist developed using this technology. Furthermore, we have solved the three-dimensional structure of the antagonist-TNFalpha complex by x-ray crystallography, and this structure is presented here. The structure has given us a unique insight into how the selection procedure works at a molecular level. Surprisingly little change is observed in the C-type lectin-like domain structure outside of the randomized regions, whereas a substantial change is observed within the randomized loops. Thus, the overall integrity of the C-type lectin-like domain is maintained, whereas specificity and binding affinity are changed by the introduction of a number of specific contacts with TNFalpha.