spacer
spacer

PDBsum entry 1ehy

Go to PDB code: 
protein metals Protein-protein interface(s) links
Hydrolase PDB id
1ehy
Jmol
Contents
Protein chains
282 a.a. *
Metals
__K ×4
Waters ×610
* Residue conservation analysis
PDB id:
1ehy
Name: Hydrolase
Title: X-ray structure of the epoxide hydrolase from agrobacterium radiobacter ad1
Structure: Protein (soluble epoxide hydrolase). Chain: a, b, c, d. Engineered: yes
Source: Agrobacterium tumefaciens. Organism_taxid: 358. Strain: ad1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.190     R-free:   0.227
Authors: M.Nardini,I.S.Ridder,H.J.Rozeboom,K.H.Kalk,R.Rink,D.B.Jansse B.W.Dijkstra
Key ref:
M.Nardini et al. (1999). The x-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1. An enzyme to detoxify harmful epoxides. J Biol Chem, 274, 14579-14586. PubMed id: 10329649 DOI: 10.1074/jbc.274.21.14579
Date:
17-Oct-98     Release date:   16-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O31243  (O31243_RHIRD) -  Epoxide hydrolase
Seq:
Struc:
294 a.a.
282 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.3.3.2.3  - Transferred entry: 3.3.2.9 and 3.3.2.10.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An epoxide + H2O = a glycol
An
+
= a
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.274.21.14579 J Biol Chem 274:14579-14586 (1999)
PubMed id: 10329649  
 
 
The x-ray structure of epoxide hydrolase from Agrobacterium radiobacter AD1. An enzyme to detoxify harmful epoxides.
M.Nardini, I.S.Ridder, H.J.Rozeboom, K.H.Kalk, R.Rink, D.B.Janssen, B.W.Dijkstra.
 
  ABSTRACT  
 
Epoxide hydrolases catalyze the cofactor-independent hydrolysis of reactive and toxic epoxides. They play an essential role in the detoxification of various xenobiotics in higher organisms and in the bacterial degradation of several environmental pollutants. The first x-ray structure of one of these, from Agrobacterium radiobacter AD1, has been determined by isomorphous replacement at 2.1-A resolution. The enzyme shows a two-domain structure with the core having the alpha/beta hydrolase-fold topology. The catalytic residues, Asp107 and His275, are located in a predominantly hydrophobic environment between the two domains. A tunnel connects the back of the active-site cavity with the surface of the enzyme and provides access to the active site for the catalytic water molecule, which in the crystal structure, has been found at hydrogen bond distance to His275. Because of a crystallographic contact, the active site has become accessible for the Gln134 side chain, which occupies a position mimicking a bound substrate. The structure suggests Tyr152/Tyr215 as the residues involved in substrate binding, stabilization of the transition state, and possibly protonation of the epoxide oxygen.
 
  Selected figure(s)  
 
Figure 6.
Fig. 6. Stereo view of the water-mediated interaction between Asp^131 and His^275 and of the oxyanion hole in epoxide hydrolase. Hydrogen bonds are shown as dashed lines. Side chains, water molecules, and the HGWP motif are in ball and stick representation. The catalytic water molecule is labeled WAT. The figure was produced using MOLSCRIPT (39).
Figure 8.
Fig. 8. Schematic representation of the catalytic mechanism of epoxide hydrolase. The Michaelis complex with epichlorohydrin is shown before the formation of covalent intermediate, which is indicated by arrows. Hydrogen bonds are shown as dashed lines.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1999, 274, 14579-14586) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20715265 A.Beloqui, J.Polaina, J.M.Vieites, D.Reyes-Duarte, R.Torres, O.V.Golyshina, T.N.Chernikova, A.Waliczek, A.Aharoni, M.M.Yakimov, K.N.Timmis, P.N.Golyshin, and M.Ferrer (2010).
Novel hybrid esterase-haloacid dehalogenase enzyme.
  Chembiochem, 11, 1975-1978.  
  20057063 C.D.Bahl, D.P.MacEachran, G.A.O'Toole, and D.R.Madden (2010).
Purification, crystallization and preliminary X-ray diffraction analysis of Cif, a virulence factor secreted by Pseudomonas aeruginosa.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 66, 26-28.  
20372740 D.O'Hagan, and J.W.Schmidberger (2010).
Enzymes that catalyse SN2 reaction mechanisms.
  Nat Prod Rep, 27, 900-918.  
19496106 B.T.Ueberbacher, G.Oberdorfer, K.Gruber, and K.Faber (2009).
Epoxide-hydrolase-initiated hydrolysis/rearrangement cascade of a methylene-interrupted bis-epoxide yields chiral THF moieties without involvement of a "cyclase".
  Chembiochem, 10, 1697-1704.  
19218394 K.Jitsumori, R.Omi, T.Kurihara, A.Kurata, H.Mihara, I.Miyahara, K.Hirotsu, and N.Esaki (2009).
X-Ray crystallographic and mutational studies of fluoroacetate dehalogenase from Burkholderia sp. strain FA1.
  J Bacteriol, 191, 2630-2637.  
19340413 M.Decker, M.Arand, and A.Cronin (2009).
Mammalian epoxide hydrolases in xenobiotic metabolism and signalling.
  Arch Toxicol, 83, 297-318.  
19547925 S.H.Choi, H.S.Kim, and E.Y.Lee (2009).
Comparative homology modeling-inspired protein engineering for improvement of catalytic activity of Mugil cephalus epoxide hydrolase.
  Biotechnol Lett, 31, 1617-1624.  
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
18058773 C.Li, M.Hassler, and T.D.Bugg (2008).
Catalytic promiscuity in the alpha/beta-hydrolase superfamily: hydroxamic acid formation, C--C bond formation, ester and thioester hydrolysis in the C--C hydrolase family.
  Chembiochem, 9, 71-76.  
19016837 D.Lindberg, A.Gogoll, and M.Widersten (2008).
Substrate-dependent hysteretic behavior in StEH1-catalyzed hydrolysis of styrene oxide derivatives.
  FEBS J, 275, 6309-6320.  
17405175 E.Y.Lee, and M.L.Shuler (2007).
Molecular engineering of epoxide hydrolase and its application to asymmetric and enantioconvergent hydrolysis.
  Biotechnol Bioeng, 98, 318-327.  
17151961 S.J.Lee, H.S.Kim, S.J.Kim, S.Park, B.J.Kim, M.L.Shuler, and E.Y.Lee (2007).
Cloning, expression and enantioselective hydrolytic catalysis of a microsomal epoxide hydrolase from a marine fish, Mugil cephalus.
  Biotechnol Lett, 29, 237-246.  
  18084077 Y.Xie, C.Takemoto, S.Kishishita, T.Uchikubo-Kamo, K.Murayama, L.Chen, Z.J.Liu, B.C.Wang, M.Manzoku, A.Ebihara, S.Kuramitsu, M.Shirouzu, and S.Yokoyama (2007).
Structure of the minimized alpha/beta-hydrolase fold protein from Thermus thermophilus HB8.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 993-997.
PDB code: 2dst
17183507 Z.Qian, C.J.Fields, Y.Yu, and S.Lutz (2007).
Recent progress in engineering alpha/beta hydrolase-fold family members.
  Biotechnol J, 2, 192-200.  
16597997 B.van Loo, J.Kingma, M.Arand, M.G.Wubbolts, and D.B.Janssen (2006).
Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis.
  Appl Environ Microbiol, 72, 2905-2917.  
  16365918 J.Jia, L.Yang, and Z.Z.Zhang (2006).
EHPred: an SVM-based method for epoxide hydrolases recognition and classification.
  J Zhejiang Univ Sci B, 7, 1-6.  
16856182 K.H.Hopmann, and F.Himo (2006).
Theoretical study of the full reaction mechanism of human soluble epoxide hydrolase.
  Chemistry, 12, 6898-6909.  
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
15822179 C.Morisseau, and B.D.Hammock (2005).
Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.
  Annu Rev Pharmacol Toxicol, 45, 311-333.  
16000814 L.Rui, L.Cao, W.Chen, K.F.Reardon, and T.K.Wood (2005).
Protein engineering of epoxide hydrolase from Agrobacterium radiobacter AD1 for enhanced activity and enantioselective production of (R)-1-phenylethane-1,2-diol.
  Appl Environ Microbiol, 71, 3995-4003.  
16213672 L.Z.Zheng, Z.Li, H.L.Tian, M.Li, and G.Q.Chen (2005).
Molecular cloning and functional analysis of (R)-3-hydroxyacyl-acyl carrier protein:coenzyme A transacylase from Pseudomonas mendocina LZ.
  FEMS Microbiol Lett, 252, 299-307.  
15146483 S.Barth, M.Fischer, R.D.Schmid, and J.Pleiss (2004).
Sequence and structure of epoxide hydrolases: a systematic analysis.
  Proteins, 55, 846-855.  
12943851 E.J.de Vries, and D.B.Janssen (2003).
Biocatalytic conversion of epoxides.
  Curr Opin Biotechnol, 14, 414-420.  
12773375 M.Arand, B.M.Hallberg, J.Zou, T.Bergfors, F.Oesch, M.J.van der Werf, J.A.de Bont, T.A.Jones, and S.L.Mowbray (2003).
Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site.
  EMBO J, 22, 2583-2592.
PDB codes: 1nu3 1nww
14517233 R.M.de Jong, J.J.Tiesinga, H.J.Rozeboom, K.H.Kalk, L.Tang, D.B.Janssen, and B.W.Dijkstra (2003).
Structure and mechanism of a bacterial haloalcohol dehalogenase: a new variation of the short-chain dehydrogenase/reductase fold without an NAD(P)H binding site.
  EMBO J, 22, 4933-4944.
PDB codes: 1pwx 1pwz 1px0
11933063 E.Shaw, L.A.McCue, C.E.Lawrence, and J.S.Dordick (2002).
Identification of a novel class in the alpha/beta hydrolase fold superfamily: the N-myc differentiation-related proteins.
  Proteins, 47, 163-168.  
11835514 J.F.Parsons, K.Lim, A.Tempczyk, W.Krajewski, E.Eisenstein, and O.Herzberg (2002).
From structure to function: YrbI from Haemophilus influenzae (HI1679) is a phosphatase.
  Proteins, 46, 393-404.
PDB codes: 1j8d 1k1e
12392563 S.Bellevik, J.Zhang, and J.Meijer (2002).
Brassica napus soluble epoxide hydrolase (BNSEH1).
  Eur J Biochem, 269, 5295-5302.  
11282336 A.Archelas, and R.Furstoss (2001).
Synthetic applications of epoxide hydrolases.
  Curr Opin Chem Biol, 5, 112-119.  
11849937 A.Steinreiber, and K.Faber (2001).
Microbial epoxide hydrolases for preparative biotransformations.
  Curr Opin Biotechnol, 12, 552-558.  
11591687 M.S.Brody, K.Vijay, and C.W.Price (2001).
Catalytic function of an alpha/beta hydrolase is required for energy stress activation of the sigma(B) transcription factor in Bacillus subtilis.
  J Bacteriol, 183, 6422-6428.  
10673439 J.Zou, B.M.Hallberg, T.Bergfors, F.Oesch, M.Arand, S.L.Mowbray, and T.A.Jones (2000).
Structure of Aspergillus niger epoxide hydrolase at 1.8 A resolution: implications for the structure and function of the mammalian microsomal class of epoxide hydrolases.
  Structure, 8, 111-122.
PDB code: 1qo7
10820034 R.Rink, J.Kingma, J.H.Lutje Spelberg, and D.B.Janssen (2000).
Tyrosine residues serve as proton donor in the catalytic mechanism of epoxide hydrolase from Agrobacterium radiobacter.
  Biochemistry, 39, 5600-5613.  
  10482514 F.Fischer, S.Künne, and S.Fetzner (1999).
Bacterial 2,4-dioxygenases: new members of the alpha/beta hydrolase-fold superfamily of enzymes functionally related to serine hydrolases.
  J Bacteriol, 181, 5725-5733.  
10485878 M.A.Argiriadi, C.Morisseau, B.D.Hammock, and D.W.Christianson (1999).
Detoxification of environmental mutagens and carcinogens: structure, mechanism, and evolution of liver epoxide hydrolase.
  Proc Natl Acad Sci U S A, 96, 10637-10642.
PDB codes: 1cqz 1cr6
10607665 M.Nardini, and B.W.Dijkstra (1999).
Alpha/beta hydrolase fold enzymes: the family keeps growing.
  Curr Opin Struct Biol, 9, 732-737.  
10404588 P.Heikinheimo, A.Goldman, C.Jeffries, and D.L.Ollis (1999).
Of barn owls and bankers: a lush variety of alpha/beta hydrolases.
  Structure, 7, R141-R146.  
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.