Preliminary time-of-flight neutron diffraction study of human deoxyhemoglobin

Human hemoglobin ( HbA) is an intricate system that has evolved to efficiently transport oxygen molecules ( O-2) from lung to tissue. Its quaternary structure can fluctuate between two conformations, T ( tense or deoxy) and R ( relaxed or oxy), which have low and high affinity for O2, respectively. The binding of O2 to the heme sites of HbA is regulated by protons and by inorganic anions. In order to investigate the role of the protonation states of protein residues in O2 binding, large crystals of deoxy HbA ( similar to 20 mm(3)) were grown in D2O under anaerobic conditions for neutron diffraction studies. A time-of-flight neutron data set was collected to 1.8 angstrom resolution on the Protein Crystallography Station ( PCS) at the spallation source run by Los Alamos Neutron Science Center ( LANSCE). The HbA tetramer ( 64.6 kDa; 574 residues excluding the four heme groups) occupies the largest asymmetric unit ( space group P2(1)) from which a high-resolution neutron data set has been collected to date.