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PDBsum entry 1s8o

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Hydrolase PDB id
1s8o
Jmol
Contents
Protein chain
545 a.a. *
Ligands
P6G
Waters ×46
* Residue conservation analysis
PDB id:
1s8o
Name: Hydrolase
Title: Human soluble epoxide hydrolase
Structure: Epoxide hydrolase 2, cytoplasmic. Chain: a. Synonym: hseh. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ephx2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: high five.
Biol. unit: Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.216     R-free:   0.272
Authors: G.A.Gomez,C.Morisseau,B.D.Hammock,D.W.Christianson
Key ref:
G.A.Gomez et al. (2004). Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis. Biochemistry, 43, 4716-4723. PubMed id: 15096040 DOI: 10.1021/bi036189j
Date:
03-Feb-04     Release date:   27-Apr-04    
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   20 terms 
  Biochemical function     catalytic activity     11 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi036189j Biochemistry 43:4716-4723 (2004)
PubMed id: 15096040  
 
 
Structure of human epoxide hydrolase reveals mechanistic inferences on bifunctional catalysis in epoxide and phosphate ester hydrolysis.
G.A.Gomez, C.Morisseau, B.D.Hammock, D.W.Christianson.
 
  ABSTRACT  
 
The X-ray crystal structure of human soluble epoxide hydrolase (sEH) has been determined at 2.6 A resolution, revealing a domain-swapped quaternary structure identical to that observed for the murine enzyme [Argiriadi, M. A., Morisseau, C., Hammock, B. D., and Christianson, D. W. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 10637-10642]. As with the murine enzyme, the epoxide hydrolytic mechanism of the human enzyme proceeds through an alkyl-enzyme intermediate with Asp-333 in the C-terminal domain. The structure of the human sEH complex with N-cyclohexyl-N'-(iodophenyl)urea (CIU) has been determined at 2.35 A resolution. Tyr-381 and Tyr-465 donate hydrogen bonds to the alkylurea carbonyl group of CIU, consistent with the proposed roles of these residues as proton donors in the first step of catalysis. The N-terminal domain of mammalian sEH contains a 15 A deep cleft, but its biological function is unclear. Recent experiments demonstrate that the N-terminal domain of human sEH catalyzes the metal-dependent hydrolysis of phosphate esters [Cronin, A., Mowbray, S., Dürk, H., Homburg, S., Fleming, I., Fisslthaler, B., Oesch, F., and Arand, M. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 1552-1557; Newman, J. W., Morisseau, C., Harris, T. R., and Hammock, B. D. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 1558-1563]. The binding of Mg(2+)-HPO4(2-) to the N-terminal domain of human sEH in its CIU complex reveals structural features relevant to those of the enzyme-substrate complex in the phosphatase reaction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21057981 Y.Sheng, C.Wei, Z.Zhang, S.Wang, and Q.Zhu (2011).
Enantioselective hydrolysis of glycidyl methylphenyl ethers by Botryosphaeria dothidea ZJUZQ007: effect of substitution pattern on enantioselectivity.
  Appl Biochem Biotechnol, 164, 125-132.  
19340413 M.Decker, M.Arand, and A.Cronin (2009).
Mammalian epoxide hydrolases in xenobiotic metabolism and signalling.
  Arch Toxicol, 83, 297-318.  
19244215 M.W.Buczynski, D.S.Dumlao, and E.A.Dennis (2009).
Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology.
  J Lipid Res, 50, 1015-1038.  
19856960 S.Lin, G.P.Horsman, Y.Chen, W.Li, and B.Shen (2009).
Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.
  J Am Chem Soc, 131, 16410-16417.  
18585390 B.K.Biswal, C.Morisseau, G.Garen, M.M.Cherney, C.Garen, C.Niu, B.D.Hammock, and M.N.James (2008).
The molecular structure of epoxide hydrolase B from Mycobacterium tuberculosis and its complex with a urea-based inhibitor.
  J Mol Biol, 381, 897-912.
PDB codes: 2e3j 2zjf
18210174 G.Melzer, S.Junne, R.Wohlgemuth, D.C.Hempel, and P.Götz (2008).
Production of epoxide hydrolases in batch fermentations of Botryosphaeria rhodina.
  J Ind Microbiol Biotechnol, 35, 485-493.  
18554159 T.R.Harris, P.A.Aronov, and B.D.Hammock (2008).
Soluble epoxide hydrolase homologs in Strongylocentrotus purpuratus suggest a gene duplication event and subsequent divergence.
  DNA Cell Biol, 27, 467-477.  
18802628 T.Y.Zakharian, L.Di Costanzo, and D.W.Christianson (2008).
Synthesis of (2S)-2-amino-7,8-epoxyoctanoic acid and structure of its metal-bridging complex with human arginase I.
  Org Biomol Chem, 6, 3240-3243.
PDB code: 3dj8
17135253 A.Luria, S.M.Weldon, A.K.Kabcenell, R.H.Ingraham, D.Matera, H.Jiang, R.Gill, C.Morisseau, J.W.Newman, and B.D.Hammock (2007).
Compensatory mechanism for homeostatic blood pressure regulation in Ephx2 gene-disrupted mice.
  J Biol Chem, 282, 2891-2898.  
17164131 B.Inceoglu, K.R.Schmelzer, C.Morisseau, S.L.Jinks, and B.D.Hammock (2007).
Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs).
  Prostaglandins Other Lipid Mediat, 82, 42-49.  
17334823 K.H.Kim (2007).
Outliers in SAR and QSAR: is unusual binding mode a possible source of outliers?
  J Comput Aided Mol Des, 21, 63-86.  
17212419 M.De Vivo, B.Ensing, M.Dal Peraro, G.A.Gomez, D.W.Christianson, and M.L.Klein (2007).
Proton shuttles and phosphatase activity in soluble epoxide hydrolase.
  J Am Chem Soc, 129, 387-394.  
17878749 N.Chiamvimonvat, C.M.Ho, H.J.Tsai, and B.D.Hammock (2007).
The soluble epoxide hydrolase as a pharmaceutical target for hypertension.
  J Cardiovasc Pharmacol, 50, 225-237.  
16908134 C.Morisseau, J.W.Newman, H.J.Tsai, P.A.Baecker, and B.D.Hammock (2006).
Peptidyl-urea based inhibitors of soluble epoxide hydrolases.
  Bioorg Med Chem Lett, 16, 5439-5444.  
16322563 G.A.Gomez, C.Morisseau, B.D.Hammock, and D.W.Christianson (2006).
Human soluble epoxide hydrolase: structural basis of inhibition by 4-(3-cyclohexylureido)-carboxylic acids.
  Protein Sci, 15, 58-64.
PDB codes: 1zd2 1zd3 1zd4 1zd5
16856182 K.H.Hopmann, and F.Himo (2006).
Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase.
  Chemistry, 12, 6898-6909.  
16870439 P.D.Jones, H.J.Tsai, Z.N.Do, C.Morisseau, and B.D.Hammock (2006).
Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase.
  Bioorg Med Chem Lett, 16, 5212-5216.  
16751602 S.L.Mowbray, L.T.Elfström, K.M.Ahlgren, C.E.Andersson, and M.Widersten (2006).
X-ray structure of potato epoxide hydrolase sheds light on substrate specificity in plant enzymes.
  Protein Sci, 15, 1628-1637.
PDB code: 2cjp
  16523628 T.R.Harris, C.Morisseau, R.L.Walzem, S.J.Ma, and B.D.Hammock (2006).
The cloning and characterization of a soluble epoxide hydrolase in chicken.
  Poult Sci, 85, 278-287.  
15822179 C.Morisseau, and B.D.Hammock (2005).
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Annu Rev Pharmacol Toxicol, 45, 311-333.  
15748653 J.W.Newman, C.Morisseau, and B.D.Hammock (2005).
Epoxide hydrolases: their roles and interactions with lipid metabolism.
  Prog Lipid Res, 44, 1.  
16142916 K.L.Tran, P.A.Aronov, H.Tanaka, J.W.Newman, B.D.Hammock, and C.Morisseau (2005).
Lipid sulfates and sulfonates are allosteric competitive inhibitors of the N-terminal phosphatase activity of the mammalian soluble epoxide hydrolase.
  Biochemistry, 44, 12179-12187.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.