1J02

Crystal Structure of Rat Heme Oxygenase-1-Heme Bound to NO

Summary for 1J02

• Entry DOI: 10.2210/pdb1j02/pdb
• Related: 1DVE 1IVJ 1IX3 1IX4 1QQ8
• Descriptor: HEME OXYGENASE 1, PROTOPORPHYRIN IX CONTAINING FE, NITRIC OXIDE, ... (4 entities in total)
• Functional Keywords: alpha helix, o2-analog bound form, oxidoreductase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Microsome: P06762
• Total number of polymer chains: 1
• Total formula weight: 31288.99

Authors

Sugishima, M.,Fukuyama, K. (deposition date: 2002-10-28, release date: 2003-09-02, Last modification date: 2023-10-25)

Primary citation

Sugishima, M.,Sakamoto, H.,Noguchi, M.,Fukuyama, K.
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 O(2) in HO-1.
Biochemistry, 42:9898-9905, 2003

PubMed Abstract: 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.

PubMed: 12924938
DOI: 10.1021/bi027268i

Experimental method

X-RAY DIFFRACTION (1.7 Å)