PDBsum entry 1dvg

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Oxidoreductase PDB id
Protein chains
214 a.a. *
HEM ×2
Waters ×143
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of rat heme oxygenase-1 in complex with heme; seleleno-methionine derivative, mutated at m51t,m93l, m155l,m191l.
Structure: Heme oxygenase-1. Chain: a, b. Synonym: ho-1. Engineered: yes. Mutation: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: expressed as residues 1-267
2.20Å     R-factor:   0.212     R-free:   0.258
Authors: M.Sugishima,Y.Omata,Y.Kakuta,H.Sakamoto,M.Noguchi,K.Fukuyama
Key ref:
M.Sugishima et al. (2000). Crystal structure of rat heme oxygenase-1 in complex with heme. FEBS Lett, 471, 61-66. PubMed id: 10760513 DOI: 10.1016/S0014-5793(00)01353-3
20-Jan-00     Release date:   12-Apr-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06762  (HMOX1_RAT) -  Heme oxygenase 1
289 a.a.
214 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 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!
  Cellular component     membrane   10 terms 
  Biological process     intracellular signal transduction   40 terms 
  Biochemical function     signal transducer activity     9 terms  


DOI no: 10.1016/S0014-5793(00)01353-3 FEBS Lett 471:61-66 (2000)
PubMed id: 10760513  
Crystal structure of rat heme oxygenase-1 in complex with heme.
M.Sugishima, Y.Omata, Y.Kakuta, H.Sakamoto, M.Noguchi, K.Fukuyama.
Heme oxygenase catalyzes the oxidative cleavage of protoheme to biliverdin, the first step of heme metabolism utilizing O(2) and NADPH. We determined the crystal structures of rat heme oxygenase-1 (HO-1)-heme and selenomethionyl HO-1-heme complexes. Heme is sandwiched between two helices with the delta-meso edge of the heme being exposed to the surface. Gly143N forms a hydrogen bond to the distal ligand of heme, OH(-). The distance between Gly143N and the ligand is shorter than that in the human HO-1-heme complex. This difference may be related to a pH-dependent change of the distal ligand of heme. Flexibility of the distal helix may control the stability of the coordination of the distal ligand to heme iron. The possible role of Gly143 in the heme oxygenase reaction is discussed.
  Selected figure(s)  
Figure 1.
Fig. 1. Ribbon diagram of rat HO-1. Only backbone and heme are displayed. Helices were named A–H sequentially from the N-terminus to the C-terminus. A: Leu13–Glu29, colored blue; B: Glu32–Gln38, colored light blue; C: Arg44–Asn68, colored green; D: Arg86–Tyr97, colored yellow green; E: Pro109–Thr124, colored yellow; F: Leu129–Met155, colored orange; G: Pro175–Met186, colored brown; and H: Pro193–Thr222, colored red. The figure was prepared with MolScript [31] and Raster3D [32].
Figure 4.
Fig. 4. Stereo view of the structures of rat and human HO-1s near the heme. Green stands for rat HO-1, blue for human HO-1 opened form and red for human HO-1 closed form. Superimpositions were carried out so as to minimize the sums of the square deviations of C[α]s. The figure was prepared with Turbo-Frodo and LSQMAN [34].
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2000, 471, 61-66) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21157922 L.Zhou, Y.Liu, C.Zou, N.Ma, Y.Hui, G.Lv, H.Zhang, H.Zhou, and X.Gao (2011).
The effect of the Gly139His, Gly143His, and Ser142His mouse heme oxygenase-1 mutants on the HO reaction in vivo and in vitro.
  Anat Rec (Hoboken), 294, 112-118.  
20378668 G.S.Shekhawat, and K.Verma (2010).
Haem oxygenase (HO): an overlooked enzyme of plant metabolism and defence.
  J Exp Bot, 61, 2255-2270.  
19697995 J.D.Belcher, J.D.Beckman, G.Balla, J.Balla, and G.Vercellotti (2010).
Heme degradation and vascular injury.
  Antioxid Redox Signal, 12, 233-248.  
20369239 M.Li, S.Noll, and J.T.Beatty (2010).
Bacteriophytochrome-dependent regulation of light-harvesting complexes in Rhodopseudomonas palustris anaerobic cultures.
  Curr Microbiol, 61, 429-434.  
19917297 N.Chim, A.Iniguez, T.Q.Nguyen, and C.W.Goulding (2010).
Unusual diheme conformation of the heme-degrading protein from Mycobacterium tuberculosis.
  J Mol Biol, 395, 595-608.
PDB code: 3hx9
19556236 H.W.Hwang, J.R.Lee, K.Y.Chou, C.S.Suen, M.J.Hwang, C.Chen, R.C.Shieh, and L.Y.Chau (2009).
Oligomerization is crucial for the stability and function of heme oxygenase-1 in the endoplasmic reticulum.
  J Biol Chem, 284, 22672-22679.  
19123922 W.J.Huber Iii, B.A.Scruggs, and W.L.Backes (2009).
C-Terminal membrane spanning region of human heme oxygenase-1 mediates a time-dependent complex formation with cytochrome P450 reductase.
  Biochemistry, 48, 190-197.  
18286277 J.D.Maréchal, and D.Perahia (2008).
Use of normal modes for structural modeling of proteins: the case study of rat heme oxygenase 1.
  Eur Biophys J, 37, 1157-1165.  
18194664 Y.Higashimoto, M.Sugishima, H.Sato, H.Sakamoto, K.Fukuyama, G.Palmer, and M.Noguchi (2008).
Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase.
  Biochem Biophys Res Commun, 367, 852-858.  
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
  17554165 M.Sugishima, K.Oda, T.Ogura, H.Sakamoto, M.Noguchi, and K.Fukuyama (2007).
Alternative cyanide-binding modes to the haem iron in haem oxygenase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 471-474.
PDB code: 2e7e
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
17428344 N.C.Rockwell, and J.C.Lagarias (2007).
Flexible mapping of homology onto structure with homolmapper.
  BMC Bioinformatics, 8, 123.  
16428411 E.P.Skaar, A.H.Gaspar, and O.Schneewind (2006).
Bacillus anthracis IsdG, a heme-degrading monooxygenase.
  J Bacteriol, 188, 1071-1080.  
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.  
16817889 P.J.Linley, M.Landsberger, T.Kohchi, J.B.Cooper, and M.J.Terry (2006).
The molecular basis of heme oxygenase deficiency in the pcd1 mutant of pea.
  FEBS J, 273, 2594-2606.  
17076701 T.Gohya, X.Zhang, T.Yoshida, and C.T.Migita (2006).
Spectroscopic characterization of a higher plant heme oxygenase isoform-1 from Glycine max (soybean)--coordination structure of the heme complex and catabolism of heme.
  FEBS J, 273, 5384-5399.  
16769893 T.Ueno, N.Yokoi, M.Unno, T.Matsui, Y.Tokita, M.Yamada, M.Ikeda-Saito, H.Nakajima, and Y.Watanabe (2006).
Design of metal cofactors activated by a protein-protein electron transfer system.
  Proc Natl Acad Sci U S A, 103, 9416-9421.
PDB codes: 1wzd 1wzf 1wzg
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.  
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
15691334 X.Zhang, C.T.Migita, M.Sato, M.Sasahara, and T.Yoshida (2005).
Protein expressed by the ho2 gene of the cyanobacterium Synechocystis sp. PCC 6803 is a true heme oxygenase. Properties of the heme and enzyme complex.
  FEBS J, 272, 1012-1022.  
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.  
15159569 H.Itou, M.Yao, N.Watanabe, and I.Tanaka (2004).
Structure analysis of PH1161 protein, a transcriptional activator TenA homologue from the hyperthermophilic archaeon Pyrococcus horikoshii.
  Acta Crystallogr D Biol Crystallogr, 60, 1094-1100.
PDB code: 1udd
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
15310749 R.Wegele, R.Tasler, Y.Zeng, M.Rivera, and N.Frankenberg-Dinkel (2004).
The heme oxygenase(s)-phytochrome system of Pseudomonas aeruginosa.
  J Biol Chem, 279, 45791-45802.  
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
15096210 X.Zhang, M.Sato, M.Sasahara, C.T.Migita, and T.Yoshida (2004).
Unique features of recombinant heme oxygenase of Drosophila melanogaster compared with those of other heme oxygenases studied.
  Eur J Biochem, 271, 1713-1724.  
14660632 Y.Li, R.T.Syvitski, K.Auclair, Montellano, and G.N.La Mar (2004).
1H NMR investigation of the solution structure of substrate-free human heme oxygenase: comparison to the cyanide-inhibited, substrate-bound complex.
  J Biol Chem, 279, 10195-10205.  
12581208 C.T.Migita, X.Zhang, and T.Yoshida (2003).
Expression and characterization of cyanobacterium heme oxygenase, a key enzyme in the phycobilin synthesis. Properties of the heme complex of recombinant active enzyme.
  Eur J Biochem, 270, 687-698.  
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
12626517 J.Wang, and Montellano (2003).
The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase.
  J Biol Chem, 278, 20069-20076.  
12794075 M.Sugishima, H.Sakamoto, Y.Higashimoto, M.Noguchi, and K.Fukuyama (2003).
Crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate. Conformational change of the distal helix during the heme cleavage reaction.
  J Biol Chem, 278, 32352-32358.
PDB code: 1j2c
14514669 Y.H.Weng, G.Yang, S.Weiss, and P.A.Dennery (2003).
Interaction between heme oxygenase-1 and -2 proteins.
  J Biol Chem, 278, 50999-51005.  
12480929 Y.Li, R.T.Syvitski, G.C.Chu, M.Ikeda-Saito, and G.N.Mar (2003).
Solution 1H NMR investigation of the active site molecular and electronic structures of substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from Corynebacterium diphtheriae.
  J Biol Chem, 278, 6651-6663.  
12230872 A.Wilks (2002).
Heme oxygenase: evolution, structure, and mechanism.
  Antioxid Redox Signal, 4, 603-614.  
12392555 H.Sakamoto, Y.Omata, S.Hayashi, S.Harada, G.Palmer, and M.Noguchi (2002).
The reactivity of alpha-hydroxyhaem and verdohaem bound to haem oxygenase-1 to dioxygen and sodium dithionite.
  Eur J Biochem, 269, 5231-5239.  
12235152 M.Sugishima, H.Sakamoto, Y.Higashimoto, Y.Omata, S.Hayashi, M.Noguchi, and K.Fukuyama (2002).
Crystal structure of rat heme oxygenase-1 in complex with heme bound to azide. Implication for regiospecific hydroxylation of heme at the alpha-meso carbon.
  J Biol Chem, 277, 45086-45090.
PDB code: 1ivj
12044160 M.Sugishima, H.Sakamoto, Y.Kakuta, Y.Omata, S.Hayashi, M.Noguchi, and K.Fukuyama (2002).
Crystal structure of rat apo-heme oxygenase-1 (HO-1): mechanism of heme binding in HO-1 inferred from structural comparison of the apo and heme complex forms.
  Biochemistry, 41, 7293-7300.
PDB code: 1irm
12070167 Y.Li, R.T.Syvitski, K.Auclair, A.Wilks, P.R.Ortiz De Montellano, and G.N.La Mar (2002).
Solution NMR characterization of an unusual distal H-bond network in the active site of the cyanide-inhibited, human heme oxygenase complex of the symmetric substrate, 2,4-dimethyldeuterohemin.
  J Biol Chem, 277, 33018-33031.  
11591684 M.Ratliff, W.Zhu, R.Deshmukh, A.Wilks, and I.Stojiljkovic (2001).
Homologues of neisserial heme oxygenase in gram-negative bacteria: degradation of heme by the product of the pigA gene of Pseudomonas aeruginosa.
  J Bacteriol, 183, 6394-6403.  
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 code is shown on the right.