PDBsum entry 1j2c

Oxidoreductase

PDB id: 1j2c

Contents

Protein chain

216 a.a. *

Ligands

BLA

Metals

_FE

Waters ×74

* Residue conservation analysis

PDB id:

1j2c

Name:

Oxidoreductase

Title:

Crystal structure of rat heme oxygenase-1 in complex with biliverdin ixalpha-iron cluster

Structure:

Heme oxygenase-1. Chain: a. Fragment: c-terminal truncated protein. Synonym: ho-1, hsp32. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.40Å R-factor: 0.194 R-free: 0.239

Authors:

M.Sugishima,H.Sakamoto,M.Noguchi,K.Fukuyama

Key ref:

M.Sugishima et al. (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. PubMed id: 12794075 DOI: 10.1074/jbc.M303682200

Date:

29-Dec-02 Release date: 02-Sep-03

Protein chain

P06762  (HMOX1_RAT) -  Heme oxygenase 1 from Rattus norvegicus

Seq: 289 a.a.

Struc: 216 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.14.18 - heme oxygenase (biliverdin-producing).
• Reaction: heme b + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = biliverdin IXalpha + CO + Fe²⁺ + 3 oxidized [NADPH--hemoprotein reductase] + 3 H2O + H⁺

heme b (Bound ligand (Het Group name = BLA) matches with 77.78% similarity) + 3 × reduced [NADPH--hemoprotein reductase] + 3 × O2 = biliverdin IXalpha + CO + Fe(2+) + 3 × oxidized [NADPH--hemoprotein reductase] + 3 × H2O + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M303682200

J Biol Chem 278:32352-32358 (2003)

PubMed id: 12794075

Crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate. Conformational change of the distal helix during the heme cleavage reaction.

M.Sugishima, H.Sakamoto, Y.Higashimoto, M.Noguchi, K.Fukuyama.

ABSTRACT

The crystal structure of rat heme oxygenase-1 in complex with biliverdin-iron chelate (biliverdin(Fe)-HO-1), the immediate precursor of the final product, biliverdin, has been determined at a 2.4-A resolution. The electron density in the heme pocket clearly showed that the tetrapyrrole ring of heme is cleaved at the alpha-meso edge. Like the heme bound to HO-1, biliverdin-iron chelate is located between the distal and proximal helices, but its accommodation state seems to be less stable in light of the disordering of the solvent-exposed propionate and vinyl groups. The middle of the distal helix is shifted away from the center of the active site in biliverdin(Fe)-HO-1, increasing the size of the heme pocket. The hydrogen-bonding interaction between Glu-29 and Gln-38, considered to restrain the orientation of the proximal helix in the heme-HO-1 complex, was lost in biliverdin(Fe)-HO-1, leading to relaxation of the helix. Biliverdin has a distorted helical conformation; the lactam oxygen atom of its pyrrole ring-A interacted with Asp-140 through a hydrogen-bonding solvent network. Because of the absence of a distal water ligand, the iron atom is five-coordinated with His-25 and four pyrrole nitrogen atoms. The coordination geometry deviates considerably from a square pyramid, suggesting that the iron may be readily dissociated. We speculate that the opened conformation of the heme pocket facilitates sequential product release, first iron then biliverdin, and that because of biliverdin's increased flexibility, iron release triggers its slow dissociation.

Selected figure(s)

Figure 2.
FIG. 2. Comparison of the heme pocket structures of biliverdin(Fe)-HO-1 and N[3]^--heme-HO-1. Ball and stick models of the heme pockets of biliverdin(Fe)-HO-1 (left) and N[3]^--heme-HO-1 (right; Protein Data Bank code 1IVJ [PDB] ). For clarity, in the F helix only main-chain atoms are shown. Dashed lines indicate hydrogen-bonds that stabilize the two conformers. Numerals show distances between atoms in Angstroms.

Figure 6.
FIG. 6. Comparison of the distal hydrogen-bond networks in biliverdin(Fe)-HO-1 (green) and N[3]^--heme-HO-1 (light blue; Protein Data Bank code 1IVJ [PDB] ). W1 through W5 indicate the water molecules in N[3]^--heme-HO-1 (17). Dashed lines indicate hydrogen-bonds (thin lines, in N[3]^--heme-HO-1; bold lines, in biliverdin(Fe)-HO-1).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 32352-32358) copyright 2003.

Figures were selected by an automated process.