PDBsum entry 1n45

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Oxidoreductase PDB id
Protein chain
214 a.a. *
HEM ×2
Waters ×425
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: X-ray crystal structure of human heme oxygenase-1 (ho-1) in complex with its substrate heme
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, ho1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
1.50Å     R-factor:   0.151     R-free:   0.217
Authors: D.J.Schuller,A.Wilks,P.R.Ortiz De Montellano,T.L.Poulos
Key ref:
L.Lad et al. (2003). Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1. J Biol Chem, 278, 7834-7843. PubMed id: 12500973 DOI: 10.1074/jbc.M211450200
30-Oct-02     Release date:   13-Nov-02    
Supersedes: 1qq8
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 = 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: 10.1074/jbc.M211450200 J Biol Chem 278:7834-7843 (2003)
PubMed id: 12500973  
Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1.
L.Lad, D.J.Schuller, H.Shimizu, J.Friedman, H.Li, P.R.Ortiz de Montellano, T.L.Poulos.
Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin. The crystal structure of human HO-1 in complex with heme reveals a novel helical structure with conserved glycines in the distal helix, providing flexibility to accommodate substrate binding and product release (Schuller, D. J., Wilks, A., Ortiz de Montellano, P. R., and Poulos, T. L. (1999) Nat. Struct. Biol. 6, 860-867). To structurally understand the HO catalytic pathway in more detail, we have determined the crystal structure of human apo-HO-1 at 2.1 A and a higher resolution structure of human HO-1 in complex with heme at 1.5 A. Although the 1.5-A heme.HO-1 model confirms our initial analysis based on the 2.08-A model, the higher resolution structure has revealed important new details such as a solvent H-bonded network in the active site that may be important for catalysis. Because of the absence of the heme, the distal and proximal helices that bracket the heme plane in the holo structure move farther apart in the apo structure, thus increasing the size of the active-site pocket. Nevertheless, the relative positioning and conformation of critical catalytic residues remain unchanged in the apo structure compared with the holo structure, but an important solvent H-bonded network is missing in the apoenzyme. It thus appears that the binding of heme and a tightening of the structure around the heme stabilize the solvent H-bonded network required for proper catalysis.
  Selected figure(s)  
Figure 9.
Fig. 9. Structural comparison between human (black) and rat (gray) apo-HO-1. A, least-squares superimposition of apo-HO-1 molecules A of rat and human; B, diagram comparing the distal and proximal heme regions; C, diagram comparing the heme pocket regions.
Figure 10.
Fig. 10. Structural comparison of the conserved H-bonding interaction surrounding Asp140 between apo-HO-1 (black) and the two conformations of heme·HO-1 (gray): closed (A) and open (B).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 7834-7843) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21283550 C.Tuzmen, and B.Erman (2011).
Identification of ligand binding sites of proteins using the gaussian network model.
  PLoS One, 6, e16474.  
20812781 S.W.Ragsdale, and L.Yi (2011).
Thiol/Disulfide redox switches in the regulation of heme binding to proteins.
  Antioxid Redox Signal, 14, 1039-1047.  
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
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.  
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
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.  
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
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.  
19694439 J.P.Evans, S.Kandel, and P.R.Ortiz de Montellano (2009).
Isocyanides inhibit human heme oxygenases at the verdoheme stage.
  Biochemistry, 48, 8920-8928.  
19587144 P.Duann, and E.A.Lianos (2009).
GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.
  Am J Physiol Renal Physiol, 297, F629-F638.  
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
17550789 D.A.Landfried, D.A.Vuletich, M.P.Pond, and J.T.Lecomte (2007).
Structural and thermodynamic consequences of b heme binding for monomeric apoglobins and other apoproteins.
  Gene, 398, 12-28.  
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
17915953 W.J.Huber, and W.L.Backes (2007).
Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.
  Biochemistry, 46, 12212-12219.  
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.  
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
15560776 P.Hlavica (2004).
Models and mechanisms of O-O bond activation by cytochrome P450. A critical assessment of the potential role of multiple active intermediates in oxidative catalysis.
  Eur J Biochem, 271, 4335-4360.  
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.