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Titolo:
A RECOMBINANT SICKLE HEMOGLOBIN TRIPLE MUTANT WITH INDEPENDENT INHIBITORY EFFECTS ON POLYMERIZATION
Autore:
HIMANEN JP; MIRZA UA; CHAIT BT; BOOKCHIN RM; MANNING JM;
Indirizzi:
NORTHEASTERN UNIV,DEPT BIOL,360 HUNTINGTON AVE BOSTON MA 02115 NORTHEASTERN UNIV,DEPT BIOL BOSTON MA 02115 ROCKEFELLER UNIV NEW YORK NY 10021 ALBERT EINSTEIN COLL MED BRONX NY 10461
Titolo Testata:
The Journal of biological chemistry
fascicolo: 41, volume: 271, anno: 1996,
pagine: 25152 - 25156
SICI:
0021-9258(1996)271:41<25152:ARSHTM>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
IN-VITRO; YEAST; SITE; CYANATE; LYSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
J.P. Himanen et al., "A RECOMBINANT SICKLE HEMOGLOBIN TRIPLE MUTANT WITH INDEPENDENT INHIBITORY EFFECTS ON POLYMERIZATION", The Journal of biological chemistry, 271(41), 1996, pp. 25152-25156

Abstract

As part of a comprehensive effort to map the most important regions of sickle hemoglobin that are involved in polymerization, we have determined whether two sites previously shown to be involved, Leu-88(beta) and Lys-95(beta), had additive effects when substituted. The former site is part of the hydrophobic pocket that binds Val-6(beta), the natural mutation of HbS, and the latter site is a prominent part of the hemoglobin exterior. A sickle hemoglobin triple mutant with three amino acid substitutions on the beta-chain, E6V/L88A/K95I, has been expressedin yeast and characterized extensively. Its oxygen binding curve, cooperativity, response to allosteric effecters, and the alkaline Bohr effect showed that it was completely functional. The polymer solubility of the deoxy triple mutant, measured by a new micromethod requiring reduced amounts of hemoglobin, was identical to that of the E6V(beta)/K95I(beta) mutant, i.e. when the K95I(beta) substitution was present on the same tetramer together with the naturally occurring E6V(beta) substitution, the L88A(beta) replacement had no additive effect on polymerinhibition. The results suggest that Lys-95(beta) on the surface of the tetramer and its complementary binding region on the adjoining tetramer are potential targets for the design of an effective antisicklingagent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 23:44:40