Showing papers by "Max F. Perutz published in 1973"
TL;DR: In this paper, the side chain of this histidine binds 2,3-diphosphoglycerate (DPG) and in normal oxyhaemoglobin it is free2,4.
Abstract: Bromberg et al. have reported interesting observations on a new abnormal haemoglobin in which histidine H21(143)β is replaced by glutamine1. In normal deoxyhaemoglobin, the side chain of this histidine binds 2,3-diphosphoglycerate (DPG) and in normal oxyhaemoglobin it is free2–4. In the absence of DPG our electron density maps show it to be free and surrounded merely by water in both the normal deoxy and oxy forms5, 6, which implies that this side chain can have no measurable effect on the oxygen affinity; yet Bromberg et al. find the oxygen affinity of haemoglobin Little Rock to be high even in the absence of DPG.
13 citations
TL;DR: A mutant with an abnormally low oxygen affinity, increased rate of methaemoglobin formation in vitro and increased lability at high temperatures, causing mild to moderate chronic haemolytic anaemia in heterozygotes is crystallized and the site of the substitution is re-examined, which is at Ala E14(70)β which is a haem contact where only alanine or serine normally occur.
Abstract: MANY abnormal haemoglobins show changed oxygen affinities. By examining the structural effects of specific amino-acid substitutions in the atomic models of oxy and deoxyhaemoglobin it has become possible to interpret such functional changes in stereochemical terms1,2. Substitutions in the interior of the subunits and especially those in the haem pocket, are liable to change the oxygen affinity, often by altering the relative stabilifies of the oxy and deoxy forms. Substitutions at the surface of the molecule, on the other hand, are always harmless, at least in heterozygotes. One exception was haemoglobin Seattle, a mutant with an abnormally low oxygen affinity, increased rate of methaemoglobin formation in vitro and increased lability at high temperatures, causing mild to moderate chronic haemolytic anaemia in heterozygotes. These abnormalities were reported to be the result of replacement of alanine E20(76)β by glutamic acid3,4. Ala E20 is external and has no contact with the haem; it is also a site that is highly variable in different species (Asn, Gin, Lys, His and Ser have all been found there5), which is against its having any functional importance. We have crystallized haemoglobin Seattle and re-examined the site of the substitution by X-ray analysis. We found it to be at Ala E14(70)β which is a haem contact where only alanine or serine normally occur. In the accompanying paper, Kurachi et al.6 show that alanine 70 is in fact replaced by aspartate.
12 citations