PDBsum entry 1s8c

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Oxidoreductase PDB id
Protein chain
214 a.a. *
Waters ×325
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of human heme oxygenase in a complex with biliverdine
Structure: Heme oxygenase 1. Chain: a, b, c, d. Synonym: ho-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hmox1, ho1, ho. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Not given
2.19Å     R-factor:   0.240     R-free:   0.280
Authors: L.Lad,J.Friedman,H.Li,B.Bhaskar,P.R.Ortiz De Montellano, T.L.Poulos
Key ref:
L.Lad et al. (2004). Crystal structure of human heme oxygenase-1 in a complex with biliverdin. Biochemistry, 43, 3793-3801. PubMed id: 15049686 DOI: 10.1021/bi035451l
02-Feb-04     Release date:   03-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
+ 3 × AH(2)
+ 3 × O(2)
Bound ligand (Het Group name = BLA)
corresponds exactly
+ 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: 10.1021/bi035451l Biochemistry 43:3793-3801 (2004)
PubMed id: 15049686  
Crystal structure of human heme oxygenase-1 in a complex with biliverdin.
L.Lad, J.Friedman, H.Li, B.Bhaskar, P.R.Ortiz de Montellano, T.L.Poulos.
Heme oxygenase oxidatively cleaves heme to biliverdin, leading to the release of iron and CO through a process in which the heme participates both as a cofactor and as a substrate. Here we report the crystal structure of the product, iron-free biliverdin, in a complex with human HO-1 at 2.19 A. Structural comparisons of the human biliverdin-HO-1 structure with its heme complex and the recently published rat HO-1 structure in a complex with the biliverdin-iron chelate [Sugishima, M., Sakamoto, H., Higashimoto, Y., Noguchi, M., and Fukuyama, K. (2003) J. Biol. Chem. 278, 32352-32358] show two major differences. First, in the absence of an Fe-His bond and solvent structure in the active site, the distal and proximal helices relax and adopt an "open" conformation which most likely encourages biliverdin release. Second, iron-free biliverdin occupies a different position and orientation relative to heme and the biliverdin-iron complex. Biliverdin adopts a more linear conformation and moves from the heme site to an internal cavity. These structural results provide insight into the rate-limiting step in HO-1 catalysis, which is product, biliverdin, release.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20157751 M.Gheidi, N.Safari, and M.Zahedi (2010).
Theoretical investigation of the ring opening process of verdoheme to biliverdin in the presence of dioxygen.
  J Mol Model, 16, 1401-1413.  
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.  
18335441 M.Bröring, S.Köhler, S.Link, O.Burghaus, C.Pietzonka, H.Kelm, and H.J.Krüger (2008).
Iron chelates of 2,2'-bidipyrrin: stable analogues of the labile iron bilins.
  Chemistry, 14, 4006-4016.  
17955269 P.R.Jamaat, N.Safari, M.Ghiasi, S.S.Naghavi, and M.Zahedi (2008).
Noninnocent effect of axial ligand on the heme degradation process: a theoretical approach to hydrolysis pathway of verdoheme to biliverdin.
  J Biol Inorg Chem, 13, 121-132.  
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
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
17534526 T.L.Poulos (2007).
The Janus nature of heme.
  Nat Prod Rep, 24, 504-510.  
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.  
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
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
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.