INVESTIGADORES
IRAZOQUI Fernando Jose
artículos
Título:
Catalytic and glycan-binding abilities of ppGalNAc-T2 are regulated
Autor/es:
ZLOCOWSKI, NATACHA; SENDRA VG; LORENZ, VIRGINIA; VILLARREAL M,; JORGE A; NUÑEZ, YOLANDA; BENNETT EP; CLAUSEN H,; NORES GA.,; IRAZOQUI FJ
Revista:
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2011 vol. 410 p. 140 - 145
ISSN:
0006-291X
Resumen:
Post-translational acetylation is an important molecular regulatory mechanism
affecting the biological activity of proteins. Polypeptide GalNAc transferases
(ppGalNAc-Ts) are a family of enzymes that catalyze initiation of mucin-type Oglycosylation.
All ppGalNAc-Ts in mammals are type II transmembrane proteins
having a Golgi lumenal region that contains a catalytic domain with
glycosyltransferase activity, and a C-terminal R-type ("ricin-like") lectin domain. We
investigated the effect of acetylation on catalytic activity of glycosyltransferase, and
on fine carbohydrate-binding specificity of the R-type lectin domain of ppGalNAc-T2.
Acetylation effect on ppGalNAc-T2 biological activity in vitro was studied using a
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
in vitro was studied using a
purified human recombinant ppGalNAc-T2. Mass spectrometric analysis of acetylated
ppGalNAc-T2 revealed seven acetylated amino acids (K103, S109, K111, K363,
S373, K521, S529); the first five are located in the catalytic domain. Specific
glycosyltransferase activity of ppGalNAc-T2 was reduced 95% by acetylation. The
last two amino acids, K521 and S529, are located in the lectin domain, and their
acetylation results in alteration of the carbohydrate-binding ability of ppGalNAc-T2.
Direct binding assays showed that acetylation of ppGalNAc-T2 enhances the
recognition to ¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.
¦ÁGalNAc residue of MUC1¦ÁGalNAc, while competitive assays showed
that acetylation modifies the fine GalNAc-binding form of the lectin domain. Taken
together, these findings clearly indicate that biological activity (catalytic capacity and
glycan-binding ability) of ppGalNAc-T2 is regulated by acetylation.