Pattern of cavities in globins: the case of human hemoglobin

Abstract In this paper we used the technique of filling with xenon atoms the hydrophobic cavities, previously referred to as packing defects, naturally present in myoglobin and hemoglobin. Our aim is to demonstrate up to which point the primary sequence is responsible for the globins’ function; and to shed light on the conservation of potential ligand docking sites and on their role in protein dynamics. In particular, we present the high resolution structures of Xe-adduct of wild type sperm whale myoglobin and for the first time those of wild type human hemoglobin and of a quadruple mutant (L(B10)Y and H(E7)Q in both α and β chains), both in deoxy form. The analysis revealed that the number and position of cavities is different in Mb and in α and β subunits, suggesting a different dynamics for ligand migration within the protein matrix. The number and position of hydrophobic cavities will be discussed also in view of the data available for other components of the globin superfamily.other grants acknowledged Italian MIUR FIRB2003 RBLA03B3KC_004