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PDBsum entry 4hai

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protein ligands metals links
Hydrolase/hydrolase inhibitor PDB id
4hai
Jmol
Contents
Protein chain
548 a.a.
Ligands
PO4
I23
Metals
_MG
Waters ×27
PDB id:
4hai
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of human soluble epoxide hydrolase complex cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.
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: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.55Å     R-factor:   0.183     R-free:   0.236
Authors: S.Pecic,S.Pakhomova,M.E.Newcomer,C.Morisseau,B.D.Hammock,Z.Z
Key ref: S.Pecic et al. (2013). Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors. Bioorg Med Chem Lett, 23, 417-421. PubMed id: 23237835
Date:
26-Sep-12     Release date:   26-Dec-12    
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.
548 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
Bound ligand (Het Group name = PO4)
corresponds exactly
      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    
 
 
Bioorg Med Chem Lett 23:417-421 (2013)
PubMed id: 23237835  
 
 
Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.
S.Pecic, S.Pakhomova, M.E.Newcomer, C.Morisseau, B.D.Hammock, Z.Zhu, A.Rinderspacher, S.X.Deng.
 
  ABSTRACT  
 
A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.