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PDBsum entry 6uml
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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
6uml

 

 

 

 

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Contents
Protein chains
1089 a.a.
338 a.a.
25 a.a.
Ligands
Y70
Metals
_ZN ×2
PDB id:
6uml
Name: Ligase
Title: Structural basis for thalidomide teratogenicity revealed by the cereblon-ddb1-sall4-pomalidomide complex
Structure: DNA damage-binding protein 1. Chain: a. Synonym: ddb p127 subunit,DNA damage-binding protein a,ddba,damage- specific DNA-binding protein 1,hbv x-associated protein 1,xap-1,uv- damaged DNA-binding factor,uv-damaged DNA-binding protein 1,uv-ddb 1, xpe-binding factor,xpe-bf,xeroderma pigmentosum group e-complementing protein,xpce. Engineered: yes. Protein cereblon.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ddb1, xap1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: crbn, ad-006. Gene: sall4, znf797. Expressed in: escherichia coli.
Resolution:
3.58Å     R-factor:   0.207     R-free:   0.267
Authors: T.L.Clayton,M.E.Matyskiela,B.E.Pagarigan,E.T.Tran,P.P.Chamberlain
Key ref: M.E.Matyskiela et al. (2020). Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex. Nat Struct Mol Biol, 27, 319-322. PubMed id: 32251415 DOI: 10.1038/s41594-020-0405-9
Date:
09-Oct-19     Release date:   15-Apr-20    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16531  (DDB1_HUMAN) -  DNA damage-binding protein 1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1140 a.a.
1089 a.a.
Protein chain
Pfam   ArchSchema ?
Q96SW2  (CRBN_HUMAN) -  Protein cereblon from Homo sapiens
Seq:
Struc: 		442 a.a.
338 a.a.
Protein chain
Pfam   ArchSchema ?
Q9UJQ4  (SALL4_HUMAN) -  Sal-like protein 4 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1053 a.a.
25 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1038/s41594-020-0405-9 Nat Struct Mol Biol 27:319-322 (2020)
PubMed id: 32251415  
 
 
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.
M.E.Matyskiela, T.Clayton, X.Zheng, C.Mayne, E.Tran, A.Carpenter, B.Pagarigan, J.McDonald, M.Rolfe, L.G.Hamann, G.Lu, P.P.Chamberlain.
 
  ABSTRACT  
 
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4CRBN E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.
 

 

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