PDBsum entry 1ozl

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Oxidoreductase PDB id
Protein chain
214 a.a. *
HEM-_NO ×2
Waters ×448
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structures of the ferric, ferrous, and ferrous-no forms of the asp140ala mutant of human heme oxygenase-1: catalytic implications
Structure: Heme oxygenase 1. Chain: a, b. Fragment: residues 1-233 of sws p09601. Synonym: ho-1. Heme oxygenase (decyclizing) 1. Engineered: yes. Mutation: yes. Other_details: heme-complexed
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hmox1. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.58Å     R-factor:   0.205     R-free:   0.222
Authors: L.Lad,J.Wang,H.Li,J.Friedman,P.R.Ortiz De Montellano, T.L.Poulos
Key ref:
L.Lad et al. (2003). Crystal structures of the ferric, ferrous, and ferrous-NO forms of the Asp140Ala mutant of human heme oxygenase-1: catalytic implications. J Mol Biol, 330, 527-538. PubMed id: 12842469 DOI: 10.1016/S0022-2836(03)00578-3
09-Apr-03     Release date:   05-Aug-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P09601  (HMOX1_HUMAN) -  Heme oxygenase 1
288 a.a.
215 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.  - 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 = 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  


DOI no: 10.1016/S0022-2836(03)00578-3 J Mol Biol 330:527-538 (2003)
PubMed id: 12842469  
Crystal structures of the ferric, ferrous, and ferrous-NO forms of the Asp140Ala mutant of human heme oxygenase-1: catalytic implications.
L.Lad, J.Wang, H.Li, J.Friedman, B.Bhaskar, P.R.Ortiz de Montellano, T.L.Poulos.
Site-directed mutagenesis studies have shown that Asp140 in both human and rat heme oxygenase-1 is critical for enzyme activity. Here, we report the D140A mutant crystal structure in the Fe(III) and Fe(II) redox states as well as the Fe(II)-NO complex as a model for the Fe(II)-oxy complex. These structures are compared to the corresponding wild-type structures. The mutant and wild-type structures are very similar, except for the distal heme pocket solvent structure. In the Fe(III) D140A mutant one water molecule takes the place of the missing Asp140 carboxylate side-chain and a second water molecule, novel to the mutant, binds in the distal pocket. Upon reduction to the Fe(II) state, the distal helix running along one face of the heme moves closer to the heme in both the wild-type and mutant structures thus tightening the active site. NO binds to both the wild-type and mutant in a bent conformation that orients the NO O atom toward the alpha-meso heme carbon atom. A network of water molecules provides a H-bonded network to the NO ligand, suggesting a possible proton shuttle pathway required to activate dioxygen for catalysis. In the wild-type structure, Asp140 exhibits two conformations, suggesting a dynamic role for Asp140 in shuttling protons from bulk solvent via the water network to the iron-linked oxy complex. On the basis of these structures, we consider why the D140A mutant is inactive as a heme oxygenase but active as a peroxidase.
  Selected figure(s)  
Figure 5.
Figure 5. The 2F[o] -F[c] electron density maps contoured at 1.5s of the wild-type and D140A Fe(II)-NO complexes. Key hydrogen bonding interactions are shown as broken lines.
Figure 7.
Figure 7. A representation for the proposed mechanism of oxygen activation in human heme oxygenase-1. Note, in the absence of a stabilizing hydrogen bond from the Asp140 side-chain to Wat1, a default peroxidase (Fe(IV)-O) intermediate is formed. Black arrows represent the interactions that enhance the hydrogen-donating ability of Wat1.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 330, 527-538) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21298303 J.Igarashi, K.Kobayashi, and A.Matsuoka (2011).
A hydrogen-bonding network formed by the B10-E7-E11 residues of a truncated hemoglobin from Tetrahymena pyriformis is critical for stability of bound oxygen and nitric oxide detoxification.
  J Biol Inorg Chem, 16, 599-609.
PDB codes: 3aq5 3aq6 3aq7 3aq8 3aq9
20218710 A.V.Soldatova, M.Ibrahim, J.S.Olson, R.S.Czernuszewicz, and T.G.Spiro (2010).
New light on NO bonding in Fe(III) heme proteins from resonance raman spectroscopy and DFT modeling.
  J Am Chem Soc, 132, 4614-4625.  
20502928 J.D.Gardner, L.Yi, S.W.Ragsdale, and T.C.Brunold (2010).
Spectroscopic insights into axial ligation and active-site H-bonding in substrate-bound human heme oxygenase-2.
  J Biol Inorg Chem, 15, 1117-1127.  
19842713 D.Peng, H.Ogura, W.Zhu, L.H.Ma, J.P.Evans, P.R.Ortiz de Montellano, and G.N.La Mar (2009).
Coupling of the distal hydrogen bond network to the exogenous ligand in substrate-bound, resting state human heme oxygenase.
  Biochemistry, 48, 11231-11242.  
19243105 H.Ogura, J.P.Evans, D.Peng, J.D.Satterlee, P.R.Ortiz de Montellano, and G.N.La Mar (2009).
The orbital ground state of the azide-substrate complex of human heme oxygenase is an indicator of distal H-bonding: implications for the enzyme mechanism.
  Biochemistry, 48, 3127-3137.  
18976815 L.H.Ma, Y.Liu, X.Zhang, T.Yoshida, and G.N.La Mar (2009).
1H NMR study of the effect of variable ligand on heme oxygenase electronic and molecular structure.
  J Inorg Biochem, 103, 10-19.  
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.  
17965015 C.M.Bianchetti, L.Yi, S.W.Ragsdale, and G.N.Phillips (2007).
Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2.
  J Biol Chem, 282, 37624-37631.
PDB codes: 2q32 2qpp 2rgz
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
16388581 J.Wang, J.P.Evans, H.Ogura, G.N.La Mar, and P.R.Ortiz de Montellano (2006).
Alteration of the regiospecificity of human heme oxygenase-1 by unseating of the heme but not disruption of the distal hydrogen bonding network.
  Biochemistry, 45, 61-73.  
16704267 L.H.Ma, Y.Liu, X.Zhang, T.Yoshida, and G.N.La Mar (2006).
1H NMR study of the magnetic properties and electronic structure of the hydroxide complex of substrate-bound heme oxygenase from Neisseria meningitidis: influence of the axial water deprotonation on the distal H-bond network.
  J Am Chem Soc, 128, 6657-6668.  
16928691 Y.Higashimoto, H.Sato, H.Sakamoto, K.Takahashi, G.Palmer, and M.Noguchi (2006).
The reactions of heme- and verdoheme-heme oxygenase-1 complexes with FMN-depleted NADPH-cytochrome P450 reductase. Electrons required for verdoheme oxidation can be transferred through a pathway not involving FMN.
  J Biol Chem, 281, 31659-31667.  
16548515 Y.Liu, L.H.Ma, X.Zhang, T.Yoshida, J.D.Satterlee, and G.N.La Mar (2006).
Characterization of the spontaneous "aging" of the heme oxygenase from the pathological bacterium Neisseria meningitidis via cleavage of the C-terminus in contact with the substrate. Implications for functional studies and the crystal structure.
  Biochemistry, 45, 3875-3886.  
15525643 J.Wang, L.Lad, T.L.Poulos, and P.R.Ortiz de Montellano (2005).
Regiospecificity determinants of human heme oxygenase: differential NADPH- and ascorbate-dependent heme cleavage by the R183E mutant.
  J Biol Chem, 280, 2797-2806.
PDB codes: 1xk2 1xk3
15690204 L.Lad, A.Koshkin, Montellano, and T.L.Poulos (2005).
Crystal structures of the G139A, G139A-NO and G143H mutants of human heme oxygenase-1. A finely tuned hydrogen-bonding network controls oxygenase versus peroxidase activity.
  J Biol Inorg Chem, 10, 138-146.
PDB codes: 1xjz 1xk0 1xk1
16115896 T.Matsui, A.Nakajima, H.Fujii, K.M.Matera, C.T.Migita, T.Yoshida, and M.Ikeda-Saito (2005).
O(2)- and H(2)O(2)-dependent verdoheme degradation by heme oxygenase: reaction mechanisms and potential physiological roles of the dual pathway degradation.
  J Biol Chem, 280, 36833-36840.  
15528205 T.Matsui, M.Furukawa, M.Unno, T.Tomita, and M.Ikeda-Saito (2005).
Roles of distal Asp in heme oxygenase from Corynebacterium diphtheriae, HmuO: A water-driven oxygen activation mechanism.
  J Biol Chem, 280, 2981-2989.
PDB codes: 1wnv 1wnw 1wnx
15516695 Y.Higashimoto, H.Sakamoto, S.Hayashi, M.Sugishima, K.Fukuyama, G.Palmer, and M.Noguchi (2005).
Involvement of NADPH in the interaction between heme oxygenase-1 and cytochrome P450 reductase.
  J Biol Chem, 280, 729-737.  
15297453 J.Wang, F.Niemevz, L.Lad, L.Huang, D.E.Alvarez, G.Buldain, T.L.Poulos, and Montellano (2004).
Human heme oxygenase oxidation of 5- and 15-phenylhemes.
  J Biol Chem, 279, 42593-42604.
PDB codes: 1s13 1t5p
15560792 M.Sugishima, C.T.Migita, X.Zhang, T.Yoshida, and K.Fukuyama (2004).
Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC 6803 in complex with heme.
  Eur J Biochem, 271, 4517-4525.
PDB code: 1we1
14966119 M.Unno, T.Matsui, G.C.Chu, M.Couture, T.Yoshida, D.L.Rousseau, J.S.Olson, and M.Ikeda-Saito (2004).
Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae: implications for heme oxygenase function.
  J Biol Chem, 279, 21055-21061.
PDB code: 1v8x
14645223 S.Hirotsu, G.C.Chu, M.Unno, D.S.Lee, T.Yoshida, S.Y.Park, Y.Shiro, and M.Ikeda-Saito (2004).
The crystal structures of the ferric and ferrous forms of the heme complex of HmuO, a heme oxygenase of Corynebacterium diphtheriae.
  J Biol Chem, 279, 11937-11947.
PDB codes: 1iw0 1iw1
12819228 J.Friedman, L.Lad, R.Deshmukh, H.Li, A.Wilks, and T.L.Poulos (2003).
Crystal structures of the NO- and CO-bound heme oxygenase from Neisseriae meningitidis. Implications for O2 activation.
  J Biol Chem, 278, 34654-34659.
PDB codes: 1p3t 1p3u 1p3v
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.