N-Glycan biosynthesis - Naegleria gruberi

N-glycans or asparagine-linked glycans are major constituents of glycoproteins in eukaryotes. N-glycans are covalently attached to asparagine with the consensus sequence of Asn-X-Ser/Thr by an N-glycosidic bond, GlcNAc b1- Asn. Biosynthesis of N-glycans begins on the cytoplasmic face of the ER membrane with the transferase reaction of UDP-GlcNAc and the lipid-like precursor P-Dol (dolichol phosphate) to generate GlcNAc a1- PP-Dol. After sequential addition of monosaccharides by ALG glycosyltransferases [MD:M00055], the N-glycan precursor is attached by the OST (oligosaccharyltransferase) complex to the polypeptide chain that is being synthesized and translocated through the ER membrane. The protein-bound N-glycan precursor is subsequently trimmed, extended, and modified in the ER and Golgi by a complex series of reactions catalyzed by membrane-bound glycosidases and glycosyltransferases. N-glycans thus synthesized are classified into three types: high-mannose type, complex type, and hybrid type. Defects in N-glycan biosynthesis lead to a variety of human diseases known as congenital disorders of glycosylation [DS:H00118 H00119].

Metabolism; Glycan biosynthesis and metabolism

Naegleria gruberi [GN:ngr]

PMID:9111134

Schutzbach JS.

The role of the lipid matrix in the biosynthesis of dolichyl-linked oligosaccharides.

Glycoconj J 14:175-82 (1997)

PMID:12200473

Oriol R, Martinez-Duncker I, Chantret I, Mollicone R, Codogno P.

Common origin and evolution of glycosyltransferases using Dol-P-monosaccharides as donor substrate.

Mol Biol Evol 19:1451-63 (2002)

PMID:12684507

Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschutter A, von Figura K, Lehle L, Korner C.

A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharide biosynthesis.

J Biol Chem 278:22498-505 (2003)

PMID:11278778

Cipollo JF, Trimble RB, Chi JH, Yan Q, Dean N.

The yeast ALG11 gene specifies addition of the terminal alpha 1,2-Man to the Man5GlcNAc2-PP-dolichol N-glycosylation intermediate formed on the cytosolic side of the endoplasmic reticulum.

J Biol Chem 276:21828-40 (2001)

PMID:15987956

Frank CG, Aebi M.

ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis.

Glycobiology 15:1156-63 (2005)

PMID:16878994

O'Reilly MK, Zhang G, Imperiali B.

In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis.

Biochemistry 45:9593-603 (2006)