Artificial allosteric systems

The artificial allosteric molecule, gable porphyrin metal complexes, were prepared by connecting two independent metal porphyrin molecules by covalent bond. The author would like to discuss mostly on allosteric mechanism of the artificial allosteric systems. Our gable porphyrin system behaves similarly to natural Hb, binding small molecules like CO, 02: or base, cooperatively. The original structure of the dimeric porphyrin, especially when they are very strongly cooperative, usually needs chemical strain between two porphyrin rings and this strain is released by the first binding of small molecule which causes coordination change of the metal porphyrin. INTRODUCTION Artificial Hb/Mb type O2 transport system as man-made allosteric molecules The basic structural difference between Hb and Mb is in their quarternary structures, tetrameric and monomeric protein, respectively. The plausible process to prepare Mb and Hb is "evolution", in which a common protein probably similar to the present Hb is converted to Hb and M b by relacing amino acid residues. The adsorption isotherms given by Hb based on the structural difference as listed in Table 1. One of the great advances in mechanistic elucidation in connection with the structural feature, was made by assuming unequal equilibrium constants for the first, second, third and fourth 02 binding to the tetrameric protein in spite of the fact that the four subunits have very similar local structures (ref. 2b.c). This progress was immediately followed by the new, greater progress made by Monod (ref. 2d), who first proposed a possibility of significant conformation change in the subunit protein, from T(tense) to R(relaxed) states. After the addition of some sophistication (stepwise T/R conversion instead of the one-step conversion originally proposed) by Koshland (ref. 2e,f), the present concept of "allosteric" mechanism became complete. TABLE 1 Proposed mechanisms in cooperativity cooperativity and allosteric system ref. Hill (1910) single step with K1 2a Adair (1925) four steps with different K's 2b Pauling (1935) K1 < K2 4 K3 < K4 2c four monotonically increasing K's, subunit interaction Monod, Wymand and Changeux (1965) T * R concerted 2d Koshland, Nemethy and Filmer (1966) T f R sequential 2e Conway and Koshland (1968) modified sequential 2f * Manuscript completed by Prof. Iwao Tabushi before he died on 22 March 1987. Typed and submitted by Dr. Shin-ichi Kugimiya 581