Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
IDENTIFICATION OF FUNCTIONAL DOMAINS WITHIN THE ALPHA-SUBUNIT AND BETA-SUBUNIT OF BETA-HEXOSAMINIDASE-A THROUGH THE EXPRESSION OF ALPHA-BETA-FUSION PROTEINS
Autore:
TSE R; WU YJ; VAVOUGIOS G; HOU YM; HINEK A; MAHURAN DJ;
Indirizzi:
HOSP SICK CHILDREN,RES INST,555 UNIV AVE TORONTO ON M5G 1X8 CANADA HOSP SICK CHILDREN,RES INST TORONTO ON M5G 1X8 CANADA UNIV TORONTO,DEPT CLIN BIOCHEM TORONTO ON M5G 2C4 CANADA
Titolo Testata:
Biochemistry
fascicolo: 33, volume: 35, anno: 1996,
pagine: 10894 - 10903
SICI:
0006-2960(1996)35:33<10894:IOFDWT>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
TAY-SACHS-DISEASE; GM2 ACTIVATOR PROTEIN; HEXB GENE; ENDOPLASMIC-RETICULUM; EXTENSIVE HOMOLOGY; LYSOSOMAL-ENZYMES; CHAIN; FIBROBLASTS; MUTATION; GANGLIOSIDOSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
R. Tse et al., "IDENTIFICATION OF FUNCTIONAL DOMAINS WITHIN THE ALPHA-SUBUNIT AND BETA-SUBUNIT OF BETA-HEXOSAMINIDASE-A THROUGH THE EXPRESSION OF ALPHA-BETA-FUSION PROTEINS", Biochemistry, 35(33), 1996, pp. 10894-10903

Abstract

There are three human beta-hexosaminidase isozymes which are composedof all possible dimeric combinations of an alpha and/or a beta subunit; A (alpha beta), B (beta beta), and S (alpha alpha). The amino acid sequences of the two subunits are 60% identical, The homology between the two chains varies with the middle > the carboxy-terminal >> the amino-terminal portions, Although dimerization is required for activity,each subunit contains its own active site and differs in its substrate specificity and thermal stability. The presence of the beta subunit in hexosaminidase A also influences the substrate specificity of the alpha subunit; e.g.. in vivo only the A heterodimer can hydrolyze G(M2)ganglioside, In this report, we localize functional regions in the two subunits by cellular expression of alpha/beta fusion proteins joinedat adjacently aligned residues. First, a chimeric alpha/beta chain was made by replacing the least well-conserved amino-terminal section ofthe beta chain with the corresponding alpha section. The biochemical characteristics of this protein were nearly identical to hexosaminidase B, Therefore, the most dissimilar regions in the subunits are not responsible for their dissimilar biochemical properties, A second fusionprotein was made that also included the more homologous middle section of the alpha chain. This protein expressed the substrate specificityunique to isozymes containing an alpha subunit (A and S). We concludethat the region responsible for the ability of the alpha subunit to bind negatively charged substrates is located within residues alpha 132-283. Interestingly, the remaining carboxy-terminal section from the beta chain, beta 316-556, was sufficient to allow this chimera to hydrolyze G(M2) ganglioside with 10% the specific activity of heterodimerichexosaminidase A, Thus, the carboxy-terminal section of each subunit is likely involved in subunit-subunit interactions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:01:58