1N3U

Crystal structure of human heme oxygenase 1 (HO-1) in complex with its substrate heme, crystal form B

Summary for 1N3U

• Entry DOI: 10.2210/pdb1n3u/pdb
• Related: 1QQ8
• Descriptor: heme oxygenase 1, CHLORIDE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• Functional Keywords: alpha helices, heme-binding site, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Microsome: P09601
• Total number of polymer chains: 2
• Total formula weight: 55136.56

Authors

Lad, L.,Schuller, D.J.,Friedman, J.P.,Li, H.,Ortiz de Montellano, P.R.,Poulos, T.L. (deposition date: 2002-10-29, release date: 2002-11-06, Last modification date: 2024-02-14)

Primary citation

Lad, L.,Schuller, D.J.,Shimizu, H.,Friedman, J.,Li, H.,Ortiz de Montellano, P.R.,Poulos, T.L.
Comparison of the heme-free and -bound crystal structures of human heme oxygenase-1
J.Biol.Chem., 278:7834-7843, 2003

PubMed Abstract: 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.

PubMed: 12500973
DOI: 10.1074/jbc.M211450200

Experimental method

X-RAY DIFFRACTION (2.58 Å)