PDBsum entry 3k2m

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protein ligands Protein-protein interface(s) links
Signaling protein/protein binding PDB id
Jmol PyMol
Protein chains
100 a.a. *
101 a.a. *
PO4 ×2
Waters ×286
* Residue conservation analysis
PDB id:
Name: Signaling protein/protein binding
Title: Crystal structure of monobody ha4/abl1 sh2 domain complex
Structure: Proto-oncogene tyrosine-protein kinase abl1. Chain: a, b. Fragment: sh2 domain (unp residues 121-232). Synonym: abelson murine leukemia viral oncogene homolog 1, p150. Engineered: yes. Monobody ha4. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: abl, abl1, jtk7. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: synthetic.
1.75Å     R-factor:   0.182     R-free:   0.221
Authors: J.B.Wojcik,E.Duguid
Key ref: J.Wojcik et al. (2010). A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain. Nat Struct Mol Biol, 17, 519-527. PubMed id: 20357770
30-Sep-09     Release date:   31-Mar-10    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1
1130 a.a.
100 a.a.
Protein chains
No UniProt id for this chain
Struc: 101 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
+ [protein]-L-tyrosine
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     protein tyrosine kinase activity     1 term  


Nat Struct Mol Biol 17:519-527 (2010)
PubMed id: 20357770  
A potent and highly specific FN3 monobody inhibitor of the Abl SH2 domain.
J.Wojcik, O.Hantschel, F.Grebien, I.Kaupe, K.L.Bennett, J.Barkinge, R.B.Jones, A.Koide, G.Superti-Furga, S.Koide.
Interactions between Src homology 2 (SH2) domains and phosphotyrosine sites regulate tyrosine kinase signaling networks. Selective perturbation of these interactions is challenging due to the high homology among the 120 human SH2 domains. Using an improved phage-display selection system, we generated a small antibody mimic (or 'monobody'), termed HA4, that bound to the Abelson (Abl) kinase SH2 domain with low nanomolar affinity. SH2 protein microarray analysis and MS of intracellular HA4 interactors showed HA4's specificity, and a crystal structure revealed how this specificity is achieved. HA4 disrupted intramolecular interactions of Abl involving the SH2 domain and potently activated the kinase in vitro. Within cells, HA4 inhibited processive phosphorylation activity of Abl and also inhibited STAT5 activation. This work provides a design guideline for highly specific and potent inhibitors of a protein interaction domain and shows their utility in mechanistic and cellular investigations.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21068165 D.Lipovsek (2011).
Adnectins: engineered target-binding protein therapeutics.
  Protein Eng Des Sel, 24, 3-9.  
21518904 R.N.Gilbreth, K.Truong, I.Madu, A.Koide, J.B.Wojcik, N.S.Li, J.A.Piccirilli, Y.Chen, and S.Koide (2011).
Isoform-specific monobody inhibitors of small ubiquitin-related modifiers engineered using structure-guided library design.
  Proc Natl Acad Sci U S A, 108, 7751-7756.
PDB code: 3qht
21524274 V.J.Ruigrok, M.Levisson, M.H.Eppink, H.Smidt, and J.van der Oost (2011).
Alternative affinity tools: more attractive than antibodies?
  Biochem J, 436, 1.  
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