Showing papers by "Max F. Perutz published in 1986"

Hemoglobin as a receptor of drugs and peptides: x-ray studies of the stereochemistry of binding

Abstract: In an attempt to establish a stereochemical rationale for the development of drugs against sickle cell anemia, human deoxyhemoglobin has been crystallized with the antihyperlipoproteinemia drug beza?brate (I), with the diuretic drug ethacrynic acid (II), with the succinyl-dipeptide (III), and with the acid (IV), and the structures of the complexes formed have been determined by X-ray analysis (detailed discussion).

Studies of haemoglobin functions by site-directed mutagenesis

Abstract: Human $\beta $-globin was synthesized in Escherichia coli as a cleavable fusion protein by using the expression vector pLcIIFX$\beta $-globin (nic$^{-}$). The authentic $\beta $-globin was liberated by digestion with blood coagulation factor X$\_{\text{a}}$ and $\alpha \_{2}\beta _{2}$ tetramers were reconstituted. The oxygen-binding properties of reconstituted haemoglobin (Hb) were essentially the same as those of human native Hb. Two mutant haemoglobins were constructed by site-directed mutagenesis. Hb Nympheas (Cys-93$\beta \rightarrow $Ser) showed a slightly increased oxygen affinity and diminished co-operativity with normal DPG (2,3-diphosphoglycerate) effect and slightly reduced alkaline Bohr effects. Hb Daphne (Cys-93$\beta \rightarrow $Ser, His-143$\beta \rightarrow $Arg) showed low co-operativity with high oxygen affinity. The alkaline Bohr effect was slightly reduced, but the DPG effect was enhanced by 50% by the His-143$\beta \rightarrow $Arg mutation.