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Biomedical subjects

M F Perutz

Publications and source records attributed to M F Perutz.

At least 127 records · Page 7Linked to original sources
PubMed1973

Structure of hemoglobin M Boston, a variant with a five-coordinated ferric heme.

X-ray analysis of the natural valency hybrid alpha(2) (+M Boston)beta(2) (deoxy) shows that the ferric iron atoms in the abnormal alpha subunits are bonded to the phenolate side chains of the tyrosines that have replaced the distal histidines; the iron atoms are displaced to the distal side of the porphyrin ring and are not bonded to the proximal histidines. The resulting changes in tertiary structure of the alpha subunits stabilize the hemoglobin tetramer in the quaternary deoxy structure, which lowers the oxygen affinity of the normal beta subunits and causes cyanosis. The strength of the bond from the ferric iron to the phenolate oxygen appears to be the main factor responsible for the many abnormal properties of hemoglobin M Boston.

Adult↗
PubMed1973

Structure of sickled erythrocytes and of sickle-cell hemoglobin fibers.

Deoxyhemoglobin from patients homozygous for sickle-cell anemia (deoxyhb S) aggregates into long straight fibers. These may extend through most of the length of the sickled cell, forming either square or hexagonally packed bundles with lattice constants of 170-180 A. Each fiber is a tube made up of six thin filaments, which are wound around the tubular surface with a helical pitch of about 3000 A. Each filament is a string of single hemoglobin molecules linked end to end at intervals of 62 A in dry and 64 A in wet fibers. Molecules in neighboring filaments are in longitudinal register so that they form flat hexagonal rings; these rings are stacked so that successive ones are rotated about the fiber axis by 7.3 degrees . The whole structure repeats after about eight rings. In this structure each molecule makes contact with four neighbors. The likely orientation of the molecules and points of contact between them are discussed. Similar filaments are also observed in normal deoxygenated erythrocytes, but in much lower concentration and aggregated into fibers of irregular diameter. No filaments appear in oxygenated sickle, or normal, adult cells, nor in oxygenated or deoxygenated fetal cells.

Anemia, Sickle Cell↗
PubMed1972

Nature of haem-haem interaction.

Haem-haem interaction consists of a change of tension at the haems, caused by a transition between two alternative quaternary structures of the protein. Dr Perutz describes how spin changes that accompany reaction with ligands alter the oxygen affinity of the haems.

Allosteric Regulation↗
PubMed1972

Noncooperativity of the dimer in the reaction of hemoglobin with oxygen (human-dissociation-equilibrium-sulfhydryl-absorption-x-ray analysis).

The theory that the alphabeta dimer is the functional unit of cooperativity in hemoglobin has been tested by determination of the oxygen equilibrium curve of stable deoxy dimers, obtained by the addition of 0.9 M MgCl(2) to human des-Arg 141alpha-hemoglobin. Cooperativity was absent in this medium, but was regained on transfer of the hemoglobin to a dilute phosphate buffer, where tetramers reformed. X-ray analysis of crystals of oxy- and deoxy-des-Arg hemoglobins showed that the removal of Arg 141alpha would leave the structure of alphabeta dimers unchanged. Nonreactivity of the sulfhydryl groups at 112beta proved that the subunits in deoxy dimers form the same contact as in oxy dimers, namely alpha(1)beta(1), and that no significant dissociation into free subunits occurs in 0.9 M MgCl(2). The absorption spectrum of the deoxy dimers corresponded to the sum of the spectra of the free deoxy alpha and beta subunits, and was different from that of the deoxy tetramer, showing the constraining salt bridges formed by the C-terminal residues in the tetramer to be necessary for the spectral changes normally observed on association of the deoxy subunits.

Amides↗