7xtl | pdb_00007xtl
Crystal structure of the C-terminal domain of human N-acetylglucosaminyltransferase IVa
Structural highlights
FunctionMGT4A_HUMAN Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains (PubMed:17006639). Involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation, thereby controlling cell-surface expression of SLC2A2 in pancreatic beta cells (By similarity).[UniProtKB:Q812G0][1] Publication Abstract from PubMedN-glycans are modified by glycosyltransferases in the endoplasmic reticulum and Golgi apparatus. N-acetylglucosaminyltransferase IV (GnT-IV) is a Golgi-localized glycosyltransferase that synthesizes complex-type N-glycans in vertebrates. This enzyme attaches N-acetylglucosamine (GlcNAc) to the alpha-1,3-linked mannose branch of the N-glycan core structure via a beta-1,4 linkage. Deficiency of this enzyme is known to cause abnormal cellular functions, making it a vital enzyme for living organisms. However, there has been no report on its three-dimensional structure to date. Here, we demonstrated that the C-terminal regions (named CBML) of human GnT-IVa and Bombyx mori ortholog have the ability to bind beta-N-acetylglucosamine. Additionally, we determined the crystal structures of human CBML, B. mori CBML, and its complex with beta-GlcNAc at 1.97, 1.47, and 1.15 A resolutions, respectively, and showed that they adopt a beta-sandwich fold, similar to carbohydrate-binding module family 32 (CBM32) proteins. The regions homologous to CBML (>/=24 percent identity) were found in GnT-IV isozymes, GnT-IVb, and GnT-IVc (known as GnT-VI), and the structure of B. mori CBML in complex with beta-GlcNAc indicated that the GlcNAc-binding residues were highly conserved among these isozymes. These residues are also conserved with the GlcNAc-binding CBM32 domain of beta-N-acetylhexosaminidase NagH from Clostridium perfringens despite the low sequence identity (<20 percent). Taken together with the phylogenetic analysis, these findings indicate that these CBMLs may be novel CBM family proteins with GlcNAc-binding ability. Crystal structure and sugar-binding ability of the C-terminal domain of N-acetylglucosaminyltransferase IV establish a new carbohydrate-binding module family.,Oka N, Mori S, Ikegaya M, Park EY, Miyazaki T Glycobiology. 2022 Sep 15. pii: 6700080. doi: 10.1093/glycob/cwac058. PMID:36106687[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
