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PDBsum entry 3hok

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
3hok
Jmol
Contents
Protein chain
214 a.a. *
Ligands
HEM ×2
Q80
Waters ×186
* Residue conservation analysis
PDB id:
3hok
Name: Oxidoreductase
Title: X-ray crystal structure of human heme oxygenase-1 with (2r, 4s)-2-[2-(4-chlorophenyl)ethyl]-2-[(1h-imidazol-1-yl) methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3- dioxolane: a novel, inducible binding mode
Structure: Heme oxygenase 1. Chain: a, b. Fragment: residues 1-233. Synonym: ho-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hmox1, ho, ho1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.19Å     R-factor:   0.226     R-free:   0.289
Authors: M.N.Rahman,Z.Jia
Key ref: M.N.Rahman et al. (2009). X-ray crystal structure of human heme oxygenase-1 with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: a novel, inducible binding mode. J Med Chem, 52, 4946-4950. PubMed id: 19601578 DOI: 10.1021/jm900434f
Date:
02-Jun-09     Release date:   28-Jul-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09601  (HMOX1_HUMAN) -  Heme oxygenase 1
Seq:
Struc:
288 a.a.
214 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.14.99.3  - Heme oxygenase (biliverdin-producing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
Protoheme
Bound ligand (Het Group name = HEM)
matches with 95.00% similarity
+ 3 × AH(2)
+ 3 × O(2)
= biliverdin
+ Fe(2+)
+ CO
+ 3 × A
+ 3 × H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     heme oxygenase (decyclizing) activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1021/jm900434f J Med Chem 52:4946-4950 (2009)
PubMed id: 19601578  
 
 
X-ray crystal structure of human heme oxygenase-1 with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane: a novel, inducible binding mode.
M.N.Rahman, J.Z.Vlahakis, D.Vukomanovic, W.A.Szarek, K.Nakatsu, Z.Jia.
 
  ABSTRACT  
 
The crystal structure of human heme oxygenase-1 (HO-1) in complex with (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4[((5-trifluoromethylpyridin-2-yl)thio)methyl]-1,3-dioxolane (4) reveals a novel, inducible binding mode. Inhibitor 4 coordinates the heme iron, with its chlorophenyl group bound in a distal hydrophobic pocket, as seen in previous structures. However, accommodation of the 5-trifluoromethylpyridin-2-yl group requires a significant shift in the proximal helix, inducing the formation of a hydrophobic pocket. This is the first example of an induced binding pocket observed in HO-1.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20555417 D.Vukomanovic, B.McLaughlin, M.N.Rahman, J.Z.Vlahakis, G.Roman, R.A.Dercho, R.T.Kinobe, M.Hum, J.F.Brien, Z.Jia, W.A.Szarek, and K.Nakatsu (2010).
Recombinant truncated and microsomal heme oxygenase-1 and -2: differential sensitivity to inhibitors.
  Can J Physiol Pharmacol, 88, 480-486.  
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