title: Hemoglobin McKees Rocks (alpha2beta2145Tyr leads to Term). A human "nonsense" mutation leading to a shortened beta-chain.
abstract: The first example of the premature termination of a polypeptide chain in man appears to be Hb McKees Rocks, beta145 Tyr leads to Term, discovered in polycythemic members of a Caucasian family. Point mutation has apparently occurred at the codon for Tyr beta145 from UAU to a "nonsense" codon, UAA or UAG, resulting in a shortened polypeptide chain with Lys 144 as its carboxyl-terminal amino acid. Evidence for this structural conclusion is the absence of tryptic peptide betaT-15 from "fingerprints" of the abnormal beta-chain, the finding of C-terminal Lys, and the similarity between the functional properties of this variant hemoglobin and those of des Tyr (145)-His(146)beta hemoglobin resulting from carboxypeptidase-A digestion of normal human hemoglobin. Hb McKees Rocks has markedly abnormal properties: its oxygen affinity is the highest of the human variants described to date; its Bohr effect is reduced; it is devoid of subunit cooperativity; and it is unaffected by 2,3-diphosphoglyceric acid. These properties are probably the consequences of decreased stability of the T quaternary conformation and are partially restored in the presence of the strong allosteric effector inositol hexaphosphate.
mesh_terms: D000328:Adult; D003062:Codon; D004163:Diphosphoglyceric Acids / Q000494:pharmacology; D006455:Hemoglobins, Abnormal; D006801:Humans; D008297:Male; D009154:Mutation; D010100:Oxygen / Q000097:blood; D010108:Oxyhemoglobins; D010375:Pedigree; D010446:Peptide Fragments / Q000097:blood; D010833:Phytic Acid / Q000494:pharmacology; D011086:Polycythemia / Q000097:blood* / Q000235:genetics; D013054:Spectrophotometry, Atomic
chemical_list: D003062:Codon; D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D010108:Oxyhemoglobins; D010446:Peptide Fragments; C011840:hemoglobin McKees Rocks; D010833:Phytic Acid; D010100:Oxygen