Queen Mary School, Nanchang University, No. 1299 Xuefu Avenue, Honggutan New District, Nanchang 330036, China.
Laboratory of Translational Medicine Research, Department of Pathology, Deyang People's Hospital, No. 173 First Section of Taishanbei Road, Jingyang District, Deyang 618000, China.
Nutrients. 2022 Apr 19;14(9):1690. doi: 10.3390/nu14091690.
The cytosolic PNGase (peptide:N-glycanase), also known as peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-d-glucosaminyl) asparagine residue (Asn, N) into a N-acetyl-β-d-glucosaminyl-amine and a peptide containing an aspartate residue (Asp, D). This enzyme (NGLY1) plays an essential role in the clearance of misfolded or unassembled glycoproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive (AR) human genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP pathway, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review uncovers the NGLY1'ssdetailed structure and its important roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.
细胞质 PNGase（肽：N-聚糖酶），也称为肽-N4-（N-乙酰-β-葡萄糖胺基）-天冬酰胺酰胺酶，是一种高度保守的糖基化酶（EC 3.5.1.52），它催化 N（4）-（乙酰-β-d-葡萄糖胺基）天冬酰胺残基（Asn，N）的非溶酶体水解，生成 N-乙酰-β-d-葡萄糖胺基-胺和含有天冬氨酸残基（Asp，D）的肽。这种酶（NGLY1）在通过内质网相关降解（ERAD）过程中清除错误折叠或未组装的糖蛋白中起着至关重要的作用。越来越多的证据还指出，NGLY1 缺乏会导致一种常染色体隐性（AR）人类遗传疾病，与异常发育和先天性糖基化缺陷有关。此外，NGLY1 的缺失会影响多种细胞途径，包括但不限于 NFE2L1 途径、Creb1/Atf1-AQP 途径、BMP 途径、AMPK 途径和 SLC12A2 离子转运体，这可能是 NGLY1 缺乏症多种临床表型的潜在原因。目前的综合综述揭示了 NGLY1 的详细结构及其在 ERAD 参与、CDDG 参与和 NGLY1 缺乏症潜在治疗中的重要作用。
