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PDBsum entry 2bng

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
2bng
Jmol
Contents
Protein chains
132 a.a. *
140 a.a. *
Metals
_CA ×2
Waters ×89
* Residue conservation analysis
PDB id:
2bng
Name: Hydrolase
Title: Structure of an m.Tuberculosis leh-like epoxide hydrolase
Structure: Mb2760. Chain: a, b, c. Synonym: leh-like epoxide hydrolase. Engineered: yes. Other_details: endogenous ligand of unknown origin bound in the active site
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Hexamer (from PDB file)
Resolution:
2.50Å     R-factor:   0.224     R-free:   0.254
Authors: P.Johansson,M.Arand,T.Unge,T.Bergfors,T.A.Jones,S.L.Mowbray
Key ref:
P.Johansson et al. (2005). Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function. J Mol Biol, 351, 1048-1056. PubMed id: 16051262 DOI: 10.1016/j.jmb.2005.06.055
Date:
24-Mar-05     Release date:   03-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O33283  (O33283_MYCTU) -  Epoxide hydrolase EphG
Seq:
Struc:
149 a.a.
132 a.a.
Protein chain
Pfam   ArchSchema ?
O33283  (O33283_MYCTU) -  Epoxide hydrolase EphG
Seq:
Struc:
149 a.a.
140 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: Chains A, B, C: E.C.3.3.2.10  - Soluble epoxide hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An epoxide + H2O = a glycol
epoxide
+ H(2)O
= glycol
   Enzyme class 3: Chains A, B, C: E.C.3.3.2.11  - Cholesterol-5,6-oxide hydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. 5,6-alpha-epoxy-5-alpha-cholestan-3-beta-ol + H2O = cholestane-3- beta,5-alpha,6-beta-triol
2. 5,6-beta-epoxy-5-beta-cholestan-3-beta-ol + H2O = cholestane-3- beta,5-alpha,6-beta-triol
5,6-alpha-epoxy-5-alpha-cholestan-3-beta-ol
+ H(2)O
= cholestane-3- beta,5-alpha,6-beta-triol
5,6-beta-epoxy-5-beta-cholestan-3-beta-ol
+ H(2)O
= cholestane-3- beta,5-alpha,6-beta-triol
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     plasma membrane   1 term 
  Biological process     epoxide metabolic process   1 term 
  Biochemical function     hydrolase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2005.06.055 J Mol Biol 351:1048-1056 (2005)
PubMed id: 16051262  
 
 
Structure of an atypical epoxide hydrolase from Mycobacterium tuberculosis gives insights into its function.
P.Johansson, T.Unge, A.Cronin, M.Arand, T.Bergfors, T.A.Jones, S.L.Mowbray.
 
  ABSTRACT  
 
Epoxide hydrolases are vital to many organisms by virtue of their roles in detoxification, metabolism and processing of signaling molecules. The Mycobacterium tuberculosis genome encodes an unusually large number of epoxide hydrolases, suggesting that they might be of particular importance to these bacteria. We report here the first structure of an epoxide hydrolase from M.tuberculosis, solved to a resolution of 2.5 A using single-wavelength anomalous dispersion (SAD) from a selenomethionine-substituted protein. The enzyme features a deep active-site pocket created by the packing of three helices onto a curved six-stranded beta-sheet. This structure is similar to a previously described limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis and unlike the alpha/beta-hydrolase fold typical of mammalian epoxide hydrolases (EH). A number of changes in the mycobacterial enzyme create a wider and deeper substrate-binding pocket than is found in its Rhodococcus homologue. Interestingly, each structure contains a different type of endogenous ligand of unknown origin bound in its active site. As a consequence of its wider substrate-binding pocket, the mycobacterial EH is capable of hydrolyzing long or bulky lipophilic epoxides such as 10,11-epoxystearic acid and cholesterol 5,6-oxide at appreciable rates, suggesting that similar compound(s) will serve as its physiological substrate(s).
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Ligands and enzymatic mechanism of Rv2740 and LEH. Substrates of potential interest for Rv2740 activity are shown in (a) and the generic EH inhibitor, valpromide, in (b). The proposed catalytic mechanism of Rv2740 is shown in (c).
Figure 3.
Figure 3. The active site. (a) Residues lining the cavity of Rv2740. (b) Comparison of the size of the substrate-binding pockets of Rv2740 (blue) and LEH (red). Solvent-accessible surfaces were generated in O, using a probe radius of 1.3 Å. Residues of Rv2740 are labeled. (c) and (d) The Rv2740 active site with electron density for endogenous ligand (12F[obs] -F[calc]| contoured at 0.4 eÅ3), using views that are similar to those in (a) and (b), respectively.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 351, 1048-1056) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
19340413 M.Decker, M.Arand, and A.Cronin (2009).
Mammalian epoxide hydrolases in xenobiotic metabolism and signalling.
  Arch Toxicol, 83, 297-318.  
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.  
18675376 H.Deng, and D.O'Hagan (2008).
The fluorinase, the chlorinase and the duf-62 enzymes.
  Curr Opin Chem Biol, 12, 582-592.  
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.  
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.