Table 1.
Selected representatives of Mammalian hemoproteins and heme-sensing proteins.
| Function | Representative hemoprotein | Number/type of heme | Axial ligand | References |
|---|---|---|---|---|
| Electron transport | Cytochrome c | 1/c-type | His, Met | Mirkin et al. (2008) |
| Cytochrome b5 | 1/b-type | His, His | Wirtz et al. (2000) | |
| Cytochrome c oxidase | 2/a-type | His/Vacant, His/His | Tsukihara et al. (1995) | |
| Cytochrome c reductase | 2/b-type, 1/c-type | His/His, His/His, His/Met | Xia et al. (1997); Zhang et al. (1998) | |
| Gas carriers | Hemoglobin | 4/b-type | His, Vacant | Park et al. (2006) |
| Myoglobin | 1/b-type | His, Vacant | Evans and Brayer (1988); Vojtechovsky et al. (1999) | |
| Catalytic activity – enzyme | Catalase I | 1/b-type | Tyr, Vacant | Putnam et al. (2000) |
| Cytochrome P450 | 1/b-type | Cys, Vacant or water | Rowland et al. (2006) | |
| Indoleamine 2,3-dioxygenase | 1/b-type | His, ligand | Sugimoto et al. (2006) | |
| NO synthase | 2/b-type | Cys, Vacant | Crane et al. (1997) | |
| Cystathionine β-synthase | 1/b-type | Cys/His | Meier et al. (2001) | |
| Tryptophan 2,3-dioxygenase | 4/b-type | His/Vacant | Zhang et al. (2007b) | |
| Transient heme binding | Heme oxygenase | 1/b-type | His, Water | Lad et al. (2003) |
| Hemopexin | 1/b-type | His/His | Paoli et al. (1999) | |
| Albumin | 1/b-type | Tyr/Vacant | Wardell et al. (2002) | |
| Heme-sensing/heme regulated | NPAS2 | 2/b-type | His/Cys or His/His, His/? | Dioum et al. (2002); Uchida et al. (2005) |
| Iron regulatory protein 2 (IRP2) | 1 | Cys/? | Jeong et al. (2004) | |
| Soluble guanylyl cyclase | 1/b-type | His/Vacant | Ma et al. (2007) |
Under physiologic conditions, heme is found mainly in the “heme pockets” of hemoproteins, characterized by a high frequency in aromatic amino acids, e.g., phenylalanine (F), tyrosine (Y) or tryptophan (W) and few or no charged amino acids (Li et al., 2011), that confer hydrophobicity, required to promote stable heme binding to hemoproteins. Five highly conserved amino acids, including histidine (H), methionine (M), cysteine (C), tyrosine (Y) and lysine (K) can act as axial heme ligands in the heme pockets of hemoproteins (Li et al., 2011). Of these, H is frequently found in hemoproteins containing heme c and heme b. Moreover, C often promotes binding of heme b, whereas M binds heme c (Fufezan et al., 2008; Li et al., 2011). Other hydrophobic amino acids such as leucine (L), isoleucine (I) and valine (V) can also create interactions with the porphyrin structure of heme, whereas arginine (R) and other positively charged amino acids interact with the negatively charged heme proprionate groups (Schneider et al., 2007).