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PDBsum entry 3koo

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protein ligands links
Hydrolase PDB id
3koo
Jmol PyMol
Contents
Protein chain
545 a.a. *
Ligands
24D
Waters ×28
* Residue conservation analysis
PDB id:
3koo
Name: Hydrolase
Title: Crystal structure of soluble epoxide hydrolase
Structure: Epoxide hydrolase 2. Chain: a. Synonym: soluble epoxide hydrolase, seh, epoxide hydratase, epoxide hydrolase, ceh. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ephx2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.79Å     R-factor:   0.218     R-free:   0.307
Authors: N.A.Farrow
Key ref: A.B.Eldrup et al. (2010). Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett, 20, 571-575. PubMed id: 19969453
Date:
13-Nov-09     Release date:   28-Apr-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P34913  (HYES_HUMAN) -  Bifunctional epoxide hydrolase 2
Seq:
Struc:
 
Seq:
Struc:
555 a.a.
545 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   18 terms 
  Biochemical function     catalytic activity     11 terms  

 

 
    reference    
 
 
Bioorg Med Chem Lett 20:571-575 (2010)
PubMed id: 19969453  
 
 
Optimization of piperidyl-ureas as inhibitors of soluble epoxide hydrolase.
A.B.Eldrup, F.Soleymanzadeh, N.A.Farrow, A.Kukulka, S.De Lombaert.
 
  ABSTRACT  
 
Inhibition of sEH is hypothesized to lead to an increase in epoxyeicosatrienoic acids resulting in the potentiation of their anti-inflammatory and vasodilatory effects. In an effort to explore sEH inhibition as an avenue for the development of vasodilatory and cardio- or renal-protective agents, a lead identified through high-throughput screening was optimized, guided by the determination of a solid state co-structure with sEH. Replacement of potential toxicophores was followed by optimization of cell-based potency and ADME properties to provide a new class of functionally potent sEH inhibitors with attractive in vitro metabolic profiles and high and sustained plasma exposures after oral administration in the rat.
 

 

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