Interaction with heme

PDB 1PP9 cytochrome bcj with inhibitor stigmatellin Note [2Fe-2S] centers interact with hemes in the other monomer. 

As in peroxidases, globins, and P450s, HO-1 has a helix over the distal surface of the heme (Figs. 16,18). In other heme proteins side chains from the distal helix provide the primary contacts with the heme as well as side chains that interact with heme ligands. In sharp contrast, the distal helix in HO-1 lies much closer to the heme such that backbone atoms form the primary heme contacts. In addition, there is no neighboring residue that could serve the same fimction as the distal His in the globins and peroxidases for interaction with iron-linked ligands. 

In related work, Martiney et al. showed that metalloporphyrins with zinc or tin were capable of inhibiting hemozoin formation in trophozoite extracts [105]. Zn(II) and Sn(IV) analogs of heme were selected for study as a result of their known competitive interactions with heme in a number of systems and their use as pharmacological photosensitizers. The order of efficacy for these metalloporphyrins was ZnDPIX>SnPPIX ZnPPIX. This order is consistent with the proposed... 

Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE, Sorrentino BP, Schuetz JD. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 2004 279 24218-24225. 

The antimalarial activity of (9) involves its interaction with heme or hemin in the parasitized erythrocyte. Molecular modeling techniques have been used to investigate how the two molecules dock, the one on the other <95MI 620-0l>. The x-ray structures of artemether (23) and hemin have been taken and modeled with the SYBYL software. It is found that, in the optimum interaction, the peroxide bridge lies close to the central iron atom of heme or hemin. It will be seen in Section... 

This hypothesis was based on the evidence that, in several experimental models, artemisinin reacts with iron ions and in particular it interacts strongly with hemin (ferriprotoporphyrin IX) and its ferrous form (ferroprotoporphyrin IX) to give covalent adducts [68]. However, two different recent evidences have weakened this postulated mode of action i) it has been recently demonstrated that, once in the parasite cell, artemisinin only scarcely accumulates within the food vacuole and, thus, a key role of its interaction with heme is unlikely [69] ii) some artemisinin derivatives that are extremely active as antimalarials show very low tendency in vitro to form carbon radicals [70]. 

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