Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Site-directed mutations of human hemoglobin at residue 35 beta: A residue at the intersection of the alpha 1 beta 1, alpha 1 beta 2, and at alpha 1 alpha 2 interfaces
Autore:
Kavanaugh, JS; Weydert, JA; Rogers, PH; Arnone, A; Hui, HL; Wierzba, AM; Kwiatkowski, LD; Paily, P; Noble, RW; Bruno, S; Mozzarelli, A;
Indirizzi:
Univ Iowa, Coll Med, Dept Biochem, Iowa City, IA 52242 USA Univ Iowa IowaCity IA USA 52242 d, Dept Biochem, Iowa City, IA 52242 USA SUNY Buffalo, Vet Adm Med Ctr, Sch Med, Dept Med & Biochem, Buffalo, NY 14215 USA SUNY Buffalo Buffalo NY USA 14215 pt Med & Biochem, Buffalo, NY 14215 USA Univ Parma, Inst Biochem Sci, I-43100 Parma, Italy Univ Parma Parma Italy I-43100 a, Inst Biochem Sci, I-43100 Parma, Italy Univ Parma, Italian Natl Inst Phys Matter, I-43100 Parma, Italy Univ Parma Parma Italy I-43100 tl Inst Phys Matter, I-43100 Parma, Italy
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 9, volume: 10, anno: 2001,
pagine: 1847 - 1855
SICI:
0961-8368(200109)10:9<1847:SMOHHA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ROTHSCHILD BETA-37 TRP->ARG; RESOLUTION X-RAY; FUNCTIONAL-PROPERTIES; QUATERNARY STRUCTURE; CRYSTAL-STRUCTURES; OXYGEN-AFFINITY; RESONANCE RAMAN; T-STATE; CHLORIDE; BINDING;
Keywords:
hemoglobin; mutant; ligand-binding kinetics; ligand affinity; X-ray crystallography; single-crystal microspectrophotometry;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Arnone, A Univ Iowa, Coll Med, Dept Biochem, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 ochem, Iowa City, IA 52242 USA
Citazione:
J.S. Kavanaugh et al., "Site-directed mutations of human hemoglobin at residue 35 beta: A residue at the intersection of the alpha 1 beta 1, alpha 1 beta 2, and at alpha 1 alpha 2 interfaces", PROTEIN SCI, 10(9), 2001, pp. 1847-1855

Abstract

Because Tyr35 beta is located at the convergence of the alpha1 beta1, alpha1 beta2, and alpha1 alpha2 interfaces in deoxyhemoglobin, it can be arguedthat mutations at this position may result in large changes in the functional properties of hemoglobin. However, only small mutation-induced changes in functional and structural properties are found for the recombinant hemoglobins beta Y35F and beta Y35A. Oxygen equilibrium-binding studies in solution, which measure the overall oxygen affinity (the p50) and the overall cooperativity (the Hill coefficient) of a hemoglobin solution, show that removing the phenolic hydroxyl group of Tyr35 beta results in small decreases in oxygen affinity and cooperativity. In contrast, removing the entire phenolic ring results in a fourfold increase in oxygen affinity and no significant change in cooperativity. The kinetics of carbon monoxide (CO) combination in solution and the oxygen-binding properties of these variants in deoxy crystals, which measure the oxygen affinity and cooperativity of just the Tquaternary structure, show that the ligand affinity of the T quaternary structure decreases in beta Y35F and increases in beta Y35A. The kinetics of CO rebinding following flash photolysis, which provides a measure of the dissociation of the liganded hemoglobin tetramer, indicates that the stability of the liganded hemoglobin tetramer is not altered in beta Y35F or beta Y35A. X-ray crystal structures of deoxy beta Y35F and beta Y35A are highly isomorphous with the structure of wild-type deoxyhemoglobin. The beta Y35F mutation repositions the carboxyl group of Asp 126 alpha1 so that it may form a more favorable interaction with the guanidinium group of Arg141 alpha2. The beta Y35A mutation results in increased mobility of the Arg141 alpha side chain, implying that the interactions between Asp126 alpha1 and Arg141 alpha2 are weakened. Therefore, the changes in the functional properties ofthese 35 beta mutants appear to correlate with subtle structural differences at the C terminus of the a-subunit.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:33:41