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PDBsum entry 3wk9

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
3wk9
Jmol
Contents
Protein chain
546 a.a.
Ligands
PO4
S0F
Metals
_MG
Waters ×65
PDB id:
3wk9
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of soluble epoxide hydrolase in complex wi fragment inhibitor
Structure: Bifunctional epoxide hydrolase 2. Chain: a. Synonym: cytosolic epoxide hydrolase 2, ceh, epoxide hydrat soluble epoxide hydrolase, seh, lipid-phosphate phosphatase engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ephx2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.205     R-free:   0.252
Authors: Y.Amano,T.Yamaguchi,E.Tanabe
Key ref: Y.Amano et al. (2014). Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography. Bioorg Med Chem, 22, 2427-2434. PubMed id: 24656800 DOI: 10.1016/j.bmc.2014.03.001
Date:
18-Oct-13     Release date:   16-Apr-14    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P34913  (HYES_HUMAN) -  Bifunctional epoxide hydrolase 2
Seq:
Struc:
 
Seq:
Struc:
555 a.a.
546 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.3.1.3.76  - Lipid-phosphate phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate + H2O = (9S,10S)- 9,10-dihydroxyoctadecanoate + phosphate
(9S,10S)-10-hydroxy-9-(phosphonooxy)octadecanoate
+ H(2)O
= (9S,10S)- 9,10-dihydroxyoctadecanoate
+ phosphate
      Cofactor: Mg(2+)
   Enzyme class 3: E.C.3.3.2.10  - Soluble epoxide hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An epoxide + H2O = a glycol
epoxide
+ H(2)O
= glycol
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     metabolic process   20 terms 
  Biochemical function     catalytic activity     11 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmc.2014.03.001 Bioorg Med Chem 22:2427-2434 (2014)
PubMed id: 24656800  
 
 
Structural insights into binding of inhibitors to soluble epoxide hydrolase gained by fragment screening and X-ray crystallography.
Y.Amano, T.Yamaguchi, E.Tanabe.
 
  ABSTRACT  
 
Soluble epoxide hydrolase (sEH) is a component of the arachidonic acid cascade and is a candidate target for therapies for hypertension or inflammation. Although many sEH inhibitors are available, their scaffolds are not structurally diverse, and knowledge of their specific interactions with sEH is limited. To obtain detailed structural information about protein-ligand interactions, we conducted fragment screening of sEH, analyzed the fragments using high-throughput X-ray crystallography, and determined 126 fragment-bound structures at high resolution. Aminothiazole and benzimidazole derivatives were identified as novel scaffolds that bind to the catalytic triad of sEH with good ligand efficiency. We further identified fragment hits that bound to subpockets of sEH called the short and long branches. The water molecule conserved in the structure plays an important role in binding to the long branch, whereas Asp496 and the main chain of Phe497 form hydrogen bonds with fragment hits in the short branch. Fragment hits and their crystal structures provide structural insights into ligand binding to sEH that will facilitate the discovery of novel and potent inhibitors of sEH.