Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preliminary studies have suggested that in Hb Dakar, histidine alpha112 was substituted by a glutamine. A re-investigation on this hemoglobin is presented in this report. A structural study has been performed using a new approach to analyse the tryptic core region of the human hemoglobin alpha chain. After tryptic digestion of the aminoethylated alpha chain, a secondary digestion of the tryptic core was carried out with chymotrypsin and with another protease, thermolysin. Analyses of the chymotryptic and thermolytic peptides indicated that the structure of Hb Dakar was identical to that of Hb Grady previously described by Huisman et al. who showed the insertion of three amino acid residues in position alpha115 or alpha118. The insertion, which was localized near two residues involved in the alpha1beta1 contact, did not produce a dissociation into dimers. Functional studies demonstrated a a slightly increased oxygen affinity, a lowered cooperativity and a normal Bohr effect. The low amount of the abnormal hemoglobin (8%) may in part be explained by a slight instability of the molecule.
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PMID:Hemoglobin Dakar = Hb Grady: demonstration by a new approach to the analysis of the tryptic core region of the alpha chain and oxygen equilibrium properties. 99 99

Selective proteolysis has been used to delineate the hemoglobin-binding site on haptoglobin heavy chain. Haptoglobin was cleaved specifically by plasmin, trypsin, chymotrypsin, staphylococcal protease, and thermolysin. Haptoglobin-hemoglobin complex was treated with these enzymes to determine which sites were protected from cleavage by the hemoglobin. The modified haptoglobins were tested for changes in their hemoglobin and hemoglobin alpha chain-binding properties. The sites of proteolytic cleavage were identified from the newly generated NH2 termini by automated Edman degradation amino acid-sequencing techniques. The results suggest that residues 128 through 131, 136 and 137, as well as 9 and 10 of the heavy chain may be involved in the binding of hemoglobin. On the other hand, residues 159 and 160, which lie in the 17-residue additional loop that is unique to haptoglobin among its homologous serine protease family, and residues 73 and 74, which lie close to the carbohydrate-binding residues, appear to be remote from the hemoglobin-binding site.
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PMID:Hemoglobin-binding site on haptoglobin probed by selective proteolysis. 621 62

Hemoglobin Milledgeville, a new hemoglobin structural variant, was identified in three members of a black American family. The oxygen affinity of blood and hemoglobin samples from the affected individuals was markedly increased (p50 O2 of whole blood 11-15 mmHg at 37 degrees C, pH 7.4), and the abnormality was associated with mild erythrocytosis. The variant hemoglobin did not separate from Hb A by electrophoresis or by chromatography or isoelectric focusing, and efforts to isolate an abnormal globin chain were also unsuccessful. The Hb A2 fraction as well as Hb A from erythrocytes of affected individuals exhibited increased oxygen affinity, indicating that the altered oxygen equilibrium was the result of a hemoglobin alpha chain abnormality. Fractionation of trypsin and chymotrypsin digests of isolated alpha chains demonstrated a single abnormal peptide representing a Pro leads to Leu substitution at alpha 44 (CD2). Properties of Hb Milledgeville include low cooperativity (n = 1.1-1.4), a normal alkaline Bohr effect (delta logp50/delta pH = -0.62), and normal interaction with 2,3-diphosphoglycerate. The alpha CD2 proline residue normally participates in the formation of the alpha 1 beta 2 subunit interface in the deoxy quaternary conformation, but not in oxyhemoglobin; the leucine substitution may produce destabilization of the deoxy conformation with a resulting shift in equilibrium toward the oxy conformation.
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PMID:Hemoglobin Milledgeville (alpha 44 (CD2) Pro leads to Leu): a new variant with increased oxygen affinity. 721 61