PDBsum entry 1s13

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Oxidoreductase PDB id
Protein chain
214 a.a. *
2FH ×2
Waters ×161
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human heme oxygenase oxidatition of alpha- and gamma-meso- phenylhemes
Structure: Heme oxygenase 1. Chain: a, b. Synonym: ho-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hmox1 or ho1 or ho. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.29Å     R-factor:   0.210     R-free:   0.250
Authors: J.Wang,F.Niemevz,L.Lad,G.Buldain,T.L.Poulos,P.R.Ortiz De Montellano
Key ref:
J.Wang et al. (2004). Human heme oxygenase oxidation of 5- and 15-phenylhemes. J Biol Chem, 279, 42593-42604. PubMed id: 15297453 DOI: 10.1074/jbc.M406346200
05-Jan-04     Release date:   24-Aug-04    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: E.C.  - Heme oxygenase (biliverdin-producing).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protoheme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O
Bound ligand (Het Group name = 2FH)
matches with 68.00% 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  


DOI no: 10.1074/jbc.M406346200 J Biol Chem 279:42593-42604 (2004)
PubMed id: 15297453  
Human heme oxygenase oxidation of 5- and 15-phenylhemes.
J.Wang, F.Niemevz, L.Lad, L.Huang, D.E.Alvarez, G.Buldain, T.L.Poulos, Montellano.
Human heme oxygenase-1 (hHO-1) catalyzes the O2-dependent oxidation of heme to biliverdin, CO, and free iron. Previous work indicated that electrophilic addition of the terminal oxygen of the ferric hydroperoxo complex to the alpha-meso-carbon gives 5-hydroxyheme. Earlier efforts to block this reaction with a 5-methyl substituent failed, as the reaction still gave biliverdin IXalpha. Surprisingly, a 15-methyl substituent caused exclusive cleavage at the gamma-meso-rather than at the normal, unsubstituted alpha-meso-carbon. No CO was formed in these reactions, but the fragment cleaved from the porphyrin eluded identification. We report here that hHO-1 cleaves 5-phenylheme to biliverdin IXalpha and oxidizes 15-phenylheme at the alpha-meso position to give 10-phenylbiliverdin IXalpha. The fragment extruded in the oxidation of 5-phenylheme is benzoic acid, one oxygen of which comes from O2 and the other from water. The 2.29- and 2.11-A crystal structures of the hHO-1 complexes with 1- and 15-phenylheme, respectively, show clear electron density for both the 5- and 15-phenyl rings in both molecules of the asymmetric unit. The overall structure of 15-phenylheme-hHO-1 is similar to that of heme-hHO-1 except for small changes in distal residues 141-150 and in the proximal Lys18 and Lys22. In the 5-phenylheme-hHO-1 structure, the phenyl-substituted heme occupies the same position as heme in the heme-HO-1 complex but the 5-phenyl substituent disrupts the rigid hydrophobic wall of residues Met34, Phe214, and residues 26-42 near the alpha-meso carbon. The results provide independent support for an electrophilic oxidation mechanism and support a role for stereochemical control of the reaction regiospecificity.
  Selected figure(s)  
Figure 11.
FIG. 11. Crystal structure of 5-hHO-1. A, stereo diagram of the 2F[o] - F[c] omit electron density contoured at 1 around 5-phenylheme of 5-hHO1. B, stereo view comparison of the backbone atoms between heme-hHO-1 (gray) and 5-hHO-1 (black). Thick lines represent regions of substantial change between the two sets of structures. C, close up stereo view of the structural change near the -meso carbon between heme-hHO-1 (gray) and 5-hHO-1 (black).
Figure 12.
FIG. 12. Scheme showing one possible mechanism for the oxidation of 5-phenylheme to biliverdin IX and benzoic acid that accounts for the observed incorporation of one oxygen from O[2] and one from H[2]O.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 42593-42604) copyright 2004.  
  Figures were selected by the author.  

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.  
19954435 G.Roman, M.N.Rahman, D.Vukomanovic, Z.Jia, K.Nakatsu, and W.A.Szarek (2010).
Heme oxygenase inhibition by 2-oxy-substituted 1-azolyl-4-phenylbutanes: effect of variation of the azole moiety. X-ray crystal structure of human heme oxygenase-1 in complex with 4-phenyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone.
  Chem Biol Drug Des, 75, 68-90.
PDB code: 3k4f
18487208 J.P.Evans, F.Niemevz, G.Buldain, and Montellano (2008).
Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme.
  J Biol Chem, 283, 19530-19539.  
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