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PDBsum entry 4gpl

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protein ligands links
Ligase/ligase inhibitor PDB id
4gpl
Jmol
Contents
Protein chain
305 a.a.
Ligands
ACE-PTR-THR-PRO-
GLU-PRO-NH2
Waters ×41
PDB id:
4gpl
Name: Ligase/ligase inhibitor
Title: Structure of cbl(tkb) bound to a phosphorylated pentapeptide
Structure: Ace-ptr-thr-pro-glu-pro, peptide inhibitor. Chain: a. Engineered: yes. E3 ubiquitin-protein ligase cbl. Chain: b. Fragment: human cbl tkb domain residues 47-351. Synonym: casitas b-lineage lymphoma proto-oncogene, proto-o cbl, ring finger protein 55, signal transduction protein cb engineered: yes
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: cbl, cbl2, rnf55. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.00Å     R-factor:   0.185     R-free:   0.248
Authors: G.Borgstahl,A.Natarajan
Key ref: E.A.Kumar et al. (2013). The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides. Sci Rep, 3, 1639. PubMed id: 23572190 DOI: 10.1038/srep01639
Date:
21-Aug-12     Release date:   18-Sep-13    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P22681  (CBL_HUMAN) -  E3 ubiquitin-protein ligase CBL
Seq:
Struc:
 
Seq:
Struc:
906 a.a.
305 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of signaling   2 terms 
  Biochemical function     signal transducer activity     4 terms  

 

 
DOI no: 10.1038/srep01639 Sci Rep 3:1639 (2013)
PubMed id: 23572190  
 
 
The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides.
E.A.Kumar, Q.Chen, S.Kizhake, C.Kolar, M.Kang, C.E.Chang, G.E.Borgstahl, A.Natarajan.
 
  ABSTRACT  
 
Solving the crystal structure of Cbl(TKB) in complex with a pentapeptide, pYTPEP, revealed that the PEP region adopted a poly-L-proline type II (PPII) helix. An unnatural amino acid termed a proline-templated glutamic acid (ptE) that constrained both the backbone and sidechain to the bound conformation was synthesized and incorporated into the pYTPXP peptide. We estimated imposing structural constraints onto the backbone and sidechain of the peptide and preorganize it to the bound conformation in solution will yield nearly an order of magnitude improvement in activity. NMR studies confirmed that the ptE-containing peptide adopts the PPII conformation, however, competitive binding studies showed an order of magnitude loss of activity. Given the emphasis that is placed on imposing structural constraints, we provide an example to support the contrary. These results point to conformational flexibility at the interface, which have implications in the design of potent Cbl(TKB)-binding peptides.