Conformational Analysis of Complex Oligosaccharides: The CICADA
Approach to the Uromodulin O-Glycans

J 2004

Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans

GIANLUCA, Cioci; Alain RIVET; Jaroslav KOCA a Serge PEREZ

Základní údaje

Originální název

Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans

Název česky

Konformační analýza složitých oligosacharidů

Autoři

GIANLUCA, Cioci; Alain RIVET; Jaroslav KOCA a Serge PEREZ

Vydání

Carbohydrate Research, 2004, 0008-6215

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.451

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/04:00010477

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000220389100005

Klíčová slova anglicky

conformational analysis; oligosaccharide; CICADA

Štítky

CICADA, conformational analysis, oligosaccharide

Změněno: 13. 2. 2005 16:42, prof. RNDr. Jaroslav Koča, DrSc.

Anotace

ORIG CZ

V originále

Uromodulin is the pregancy associated Tamm-Horsfall glycoprotein, with ability to inhibit T-cell proliferation. Pregnancy-associated structural changes mainly occur in the O-glycosylation of this glycoprotein. These include up to 12 glycan structures, made up of an unusual core type 2 sequence terminated with one, two, or three sialyl Lewisx sequences; they could serve as E- and P-selectin ligands. The present work focuses on the most complex one; a tetradecamer made up of a type 2 core carrying three sialyl Lewisx branches. Five monosaccharides are assembled by fourteen glycosidic linkages. The conformational behaviour of the constituting disaccharide segments was evaluated using the flexible residue procedure of the MM3 molecular mechanics procedure. For each disaccharide, the adiabatic energy surface, along with the local energy minima have been established. All these results were used for the generation, prior to complete optimization of the tetradecamer. This was followed by a complete exploration of conformational hyperspace throughout the use of Single Coordinate Method as implemented in the CICADA program. Despite the potential flexibility of the tetradecasaccharide, only four conformational families occur, accounting for more than 95% of the total low energy conformations. For each family, the molecular properties (electrostatic, lipophilicity and hydrogen potential) have been studied. The shape of the tetradecasaccharide is best described as a flat ribbon, flanked by three branches having terminal sialyl residues. Two of the branches interact through non-bonded interactions, bringing further energy stabilization, and limiting the conformational flexibility of the sialyl residues. Only one branch maintains the original conformational features of sialyl Lewisx. The O-glycan can be seen as a fascinating example of dendrimeric structure, where the spatial arrangement of three S-Lex epitopes throughout their complementary presentations for interactions with E- and P-selectins.

Česky

Konformační analýza složitých oligosacharidů

Návaznosti

MSM 143100005, záměr

Název: Strukturně-funkční vztahy biomolekul a jejich role v metabolismu

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Strukturně-funkční vztahy biomolekul a jejich role v metabolismu

Citovat

GIANLUCA, Cioci; Alain RIVET; Jaroslav KOCA a Serge PEREZ. Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans. Carbohydrate Research. 2004, roč. 339, č. 4, s. 949-959. ISSN 0008-6215.

@article{560826,
   author = {Gianluca, Cioci and Rivet, Alain and Koca, Jaroslav and Perez, Serge},
   article_number = {4},
   keywords = {conformational analysis; oligosaccharide; CICADA},
   language = {eng},
   issn = {0008-6215},
   journal = {Carbohydrate Research},
   title = {Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans},
   volume = {339},
   year = {2004}
}

TY  - JOUR
ID  - 560826
AU  - Gianluca, Cioci - Rivet, Alain - Koca, Jaroslav - Perez, Serge
PY  - 2004
TI  - Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans
JF  - Carbohydrate Research
VL  - 339
IS  - 4
SP  - 949-959
EP  - 949-959
SN  - 00086215
KW  - conformational analysis
KW  - oligosaccharide
KW  - CICADA
N2  - Uromodulin is the pregancy associated Tamm-Horsfall glycoprotein, with ability to inhibit T-cell proliferation. Pregnancy-associated structural changes mainly occur in the O-glycosylation of this glycoprotein. These include up to 12 glycan structures, made up of an unusual core type 2 sequence terminated with one, two, or three sialyl Lewisx sequences; they could serve as E- and P-selectin ligands. The present work focuses on the most complex one; a tetradecamer made up of a type 2 core carrying three sialyl Lewisx branches. Five monosaccharides are assembled by fourteen glycosidic linkages. The conformational behaviour of the constituting disaccharide segments was evaluated using the flexible residue procedure of the MM3 molecular mechanics procedure. For each disaccharide, the adiabatic energy surface, along with the local energy minima have been established. All these results were used for the generation, prior to complete optimization of the tetradecamer. This was followed by a complete exploration of conformational hyperspace throughout the use of Single Coordinate Method as implemented in the CICADA program. Despite the potential flexibility of the tetradecasaccharide, only four conformational families occur, accounting for more than 95% of the total low energy conformations. For each family, the molecular properties (electrostatic, lipophilicity and hydrogen potential) have been studied. The shape of the tetradecasaccharide is best described as a flat ribbon, flanked by three branches having terminal sialyl residues. Two of the branches interact through non-bonded interactions, bringing further energy stabilization, and limiting the conformational flexibility of the sialyl residues. Only one branch maintains the original conformational features of sialyl Lewisx. The O-glycan can be seen as a fascinating example of dendrimeric structure, where the spatial arrangement of three S-Lex epitopes throughout their complementary presentations for interactions with E- and P-selectins.
ER  -

GIANLUCA, Cioci; Alain RIVET; Jaroslav KOCA a Serge PEREZ. Conformational Analysis of Complex Oligosaccharides: The CICADA Approach to the Uromodulin O-Glycans. \textit{Carbohydrate Research}. 2004, roč.~339, č.~4, s.~949-959. ISSN~0008-6215.

Přehled o publikaci