PDBsum entry 1ubb

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Oxidoreductase PDB id
Protein chain
212 a.a. *
Waters ×155
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of rat ho-1 in complex with ferrous heme
Structure: Heme oxygenase 1. Chain: a. Fragment: c-terminal truncated ho-1. Synonym: ho-1. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.30Å     R-factor:   0.185     R-free:   0.220
Authors: M.Sugishima,H.Sakamoto,Y.Higashimoto,M.Noguchi,K.Fukuyama
Key ref:
M.Sugishima et al. (2003). Crystal structures of ferrous and CO-, CN(-)-, and NO-bound forms of rat heme oxygenase-1 (HO-1) in complex with heme: structural implications for discrimination between CO and O2 in HO-1. Biochemistry, 42, 9898-9905. PubMed id: 12924938 DOI: 10.1021/bi027268i
03-Apr-03     Release date:   02-Sep-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06762  (HMOX1_RAT) -  Heme oxygenase 1
289 a.a.
212 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 = 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: 10.1021/bi027268i Biochemistry 42:9898-9905 (2003)
PubMed id: 12924938  
Crystal structures of ferrous and CO-, CN(-)-, and NO-bound forms of rat heme oxygenase-1 (HO-1) in complex with heme: structural implications for discrimination between CO and O2 in HO-1.
M.Sugishima, H.Sakamoto, M.Noguchi, K.Fukuyama.
Heme oxygenase (HO) catalyzes heme degradation by utilizing O(2) and reducing equivalents to produce biliverdin IX alpha, iron, and CO. To avoid product inhibition, the heme[bond]HO complex (heme[bond]HO) is structured to markedly increase its affinity for O(2) while suppressing its affinity for CO. We determined the crystal structures of rat ferrous heme[bond]HO and heme[bond]HO bound to CO, CN(-), and NO at 2.3, 1.8, 2.0, and 1.7 A resolution, respectively. The heme pocket of ferrous heme-HO has the same conformation as that of the previously determined ferric form, but no ligand is visible on the distal side of the ferrous heme. Fe[bond]CO and Fe[bond]CN(-) are tilted, whereas the Fe[bond]NO is bent. The structure of heme[bond]HO bound to NO is identical to that bound to N(3)(-), which is also bent as in the case of O(2). Notably, in the CO- and CN(-)-bound forms, the heme and its ligands shift toward the alpha-meso carbon, and the distal F-helix shifts in the opposite direction. These shifts allow CO or CN(-) to bind in a tilted fashion without a collision between the distal ligand and Gly139 O and cause disruption of one salt bridge between the heme and basic residue. The structural identity of the ferrous and ferric states of heme[bond]HO indicates that these shifts are not produced on reduction of heme iron. Neither such conformational changes nor a heme shift occurs on NO or N(3)(-) binding. Heme[bond]HO therefore recognizes CO and O(2) by their binding geometries. The marked reduction in the ratio of affinities of CO to O(2) for heme[bond]HO achieved by an increase in O(2) affinity [Migita, C. T., Matera, K. M., Ikeda-Saito, M., Olson, J. S., Fujii, H., Yoshimura, T., Zhou, H., and Yoshida, T. (1998) J. Biol. Chem. 273, 945-949] is explained by hydrogen bonding and polar interactions that are favorable for O(2) binding, as well as by characteristic structural changes in the CO-bound form.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19939208 M.Kajimura, R.Fukuda, R.M.Bateman, T.Yamamoto, and M.Suematsu (2010).
Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology.
  Antioxid Redox Signal, 13, 157-192.  
20606257 Serrano, M.F.Davis, J.F.Gaff, Q.Zhang, Z.Chen, E.L.D'Antonio, E.F.Bowden, R.Rose, and S.Franzen (2010).
X-ray structure of the metcyano form of dehaloperoxidase from Amphitrite ornata: evidence for photoreductive dissociation of the iron-cyanide bond.
  Acta Crystallogr D Biol Crystallogr, 66, 770-782.
PDB codes: 3kun 3kuo
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.  
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
17095508 J.Friedman, Y.T.Meharenna, A.Wilks, and T.L.Poulos (2007).
Diatomic ligand discrimination by the heme oxygenases from Neisseria meningitidis and Pseudomonas aeruginosa.
  J Biol Chem, 282, 1066-1071.  
17372351 K.Fukuyama, and T.Okada (2007).
Structures of cyanide, nitric oxide and hydroxylamine complexes of Arthromyces ramosusperoxidase at 100 K refined to 1.3 A resolution: coordination geometries of the ligands to the haem iron.
  Acta Crystallogr D Biol Crystallogr, 63, 472-477.
PDB codes: 2e39 2e3a 2e3b
  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.  
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.  
16683803 L.H.Ma, Y.Liu, X.Zhang, T.Yoshida, K.C.Langry, K.M.Smith, and G.N.La Mar (2006).
Modulation of the axial water hydrogen-bonding properties by chemical modification of the substrate in resting state, substrate-bound heme oxygenase from Neisseria meningitidis; coupling to the distal H-bond network via ordered water molecules.
  J Am Chem Soc, 128, 6391-6399.  
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.  
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
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.  
15528039 F.J.Cronje, M.S.Carraway, J.J.Freiberger, H.B.Suliman, and C.A.Piantadosi (2004).
Carbon monoxide actuates O(2)-limited heme degradation in the rat brain.
  Free Radic Biol Med, 37, 1802-1812.  
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
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.