Heme proteins have a surprisingly large array of functions, including electron transfer, oxygen transport, NO sensing, oxidant detoxification, and 0(2) activation. The protein provides one or two sites for ligation of the metalloporphyrin and multiple peripheral interactions (covalent, hydrophobic, hydrogen-bonding, or ion-pairing) so that the heme is bound to the protein very tightly. The protein environment also fine-tunes the reactivity of the metalloporphyrin. Designing minimal peptides as analogues of heme proteins, we have prepared a series of helical 15-mer peptides that bind strongly to metalloporphyrins and succeeded in solving their solution NMR structures. Interestingly, the structures show that the helix is tilted toward one side of the porphyrin so as to maximize hydrophobic interaction between the peptide and one-half of the porphyrin face. Because of this asymmetry, only three hydrophobic residues are in primary contact with the porphyrin, as confirmed by the NOE signals between the porphyrin meso- protons and beta-protons of these residues. Such helix tilt is very common in heme proteins, including cytochrome c peroxidase, cytochrome b(562), and myoglobin. The heme therefore has not only a functional role in heme proteins, but also plays a profound structural role in the stabilization of secondary structure and helix orientation.