Last update 19 Sep 2024

FUCA1

Last update 19 Sep 2024

Basic Info

Synonyms

alpha-L-fucosidase 1, Alpha-L-fucosidase I, Alpha-L-fucoside fucohydrolase 1

+ [2]

Introduction

Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.

Drugs associated with FUCA1

GRI-2

Target

FUCA1

Mechanism

FUCA1 modulators

Active Org.-

Originator Org.

Allelix Neuroscience, Inc.

Active Indication-

Inactive Indication

Muscle Hypertonia

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FUCA1

100 Translational Medicine associated with FUCA1

0 Patents (Medical) associated with FUCA1

1,071

Literatures (Medical) associated with FUCA1

01 Nov 2024·Gene

Potential predictive value of immune-related genes FUCA1 and NCKAP1L for osteosarcoma metastasis

Article

Author: Dou, Junzhe ; Liu, Maorong ; Tong, Zhichao ; Zhang, Yunheng ; Wang, Xuan ; Li, Yi

BACKGROUNDOsteosarcoma is a common malignant tumor with a low survival rate after metastasis. Current treatments have not proven to effectively increase patient survival rates. Immunotherapy is a promising new treatment approach, however, immune target therapy has not shown satisfactory results. This study aims to provide new insights and evidence for the use of immunotherapy in osteosarcoma, based on a comprehensive analysis of gene expression data from databases.METHODSGene expression and GSAV analysis were conducted on samples from patients with metastatic and non-metastatic osteosarcoma in the TARGET and GEO databases to identify relevant genes. These genes were further analyzed using GO, KEGG, GSVA, correlation analysis, and immune microenvironment scoring techniques. The tissue location of gene expression was confirmed through single-cell analysis. Validation of gene expression patterns was performed using polymerase chain reaction, western blot, and immunohistochemistry.RESULTSThe study identified FUCA1 and NCKAP1L as significantly enriched in non-metastatic osteosarcoma, with higher expression associated with better patient survival rates. Gene function enrichment was primarily related to immune functions, with positive correlations to macrophage phagocytosis, antigen presentation, and macrophage polarization pathways. Analysis of the immune microenvironment revealed a positive correlation between gene expression and immune scores, with increased presence of macrophages, T cells, and B cells in the high expression group. Single-cell analysis and experimental results confirmed the enrichment of FUCA1 and NCKAP1L in macrophages.CONCLUSIONThe identification of FUCA1 and NCKAP1L as potential prognostic biomarkers suggests their potential for improving patient outcomes. Modulation of macrophages may offer a promising strategy for enhancing the immune microenvironment in osteosarcoma.

14 Aug 2024·mBio

Ruminococcus torques is a keystone degrader of intestinal mucin glycoprotein, releasing oligosaccharides used by Bacteroides thetaiotaomicron

Article

Author: Madlambayan, Emily ; Schaus, Sadie R ; Terrapon, Nicolas ; Henrissat, Bernard ; Hansson, Gunnar C ; Martens, Eric C ; Luis, Ana S ; Vasconcelos Pereira, Gabriel ; Ostrowski, Matthew P ; Jin, Chunsheng

ABSTRACT Symbiotic interactions between humans and our communities of resident gut microbes (microbiota) play many roles in health and disease. Some gut bacteria utilize mucus as a nutrient source and can under certain conditions damage the protective barrier it forms, increasing disease susceptibility. We investigated how Ruminococcus torques— a known mucin degrader that has been implicated in inflammatory bowel diseases (IBDs)—degrades mucin glycoproteins or their component O -linked glycans to understand its effects on the availability of mucin-derived nutrients for other bacteria. We found that R. torques utilizes both mucin glycoproteins and released oligosaccharides from gastric and colonic mucins, degrading these substrates with a panoply of mostly constitutively expressed, secreted enzymes. Investigation of mucin oligosaccharide degradation by R. torques revealed strong α-L-fucosidase, sialidase and β1,4-galactosidase activities. There was a lack of detectable sulfatase and weak β1,3-galactosidase degradation, resulting in accumulation of glycans containing these structures on mucin polypeptides. While the Gram-negative symbiont, Bacteroides thetaiotaomicron grows poorly on mucin glycoproteins, we demonstrate a clear ability of R. torques to liberate products from mucins, making them accessible to B. thetaiotaomicron . This work underscores the diversity of mucin-degrading mechanisms in different bacterial species and the probability that some species are contingent on others for the ability to more fully access mucin-derived nutrients. The ability of R. torques to directly degrade a variety of mucin and mucin glycan structures and unlock released glycans for other species suggests that it is a keystone mucin degrader, which might contribute to its association with IBD. IMPORTANCE An important facet of maintaining healthy symbiosis between host and intestinal microbes is the mucus layer, the first defense protecting the epithelium from lumenal bacteria. Some gut bacteria degrade the various components of intestinal mucins, but detailed mechanisms used by different species are still emerging. It is imperative to understand these mechanisms as they likely dictate interspecies interactions and may illuminate species associated with bacterial mucus damage and subsequent disease susceptibility. Ruminococcus torques is positively associated with IBD in multiple studies. We identified mucin glycan-degrading enzymes in R. torques and found that it shares mucin degradation products with another species of gut bacteria, Bacteroides thetaiotaomicron . Our findings underscore the importance of understanding mucin degradation mechanisms in different gut bacteria and their consequences on interspecies interactions, which may identify keystone bacteria that disproportionately affect mucus damage and could therefore be key players in effects that result from reductions in mucus integrity.

19 Jul 2024·ACS Chemical Biology

A Robust α-l-Fucosidase from Prevotella nigrescens for Glycoengineering Therapeutic Antibodies

Article

Author: Kao, Mu-Rong ; Chou, Hsiang-Yu ; Liao, Kuo-Shiang ; Chang, Shu-Chieh ; Cheng, Lin-Chen ; Ma, Tzu-Hsuan ; Shie, Jiun-Jie ; Wong, Chi-Huey ; Hsieh, Yves S Y ; Harris, Philip J

Eliminating the core fucose from the N-glycans of the Fc antibody segment by pathway engineering or enzymatic methods has been shown to enhance the potency of therapeutic antibodies, especially in the context of antibody-dependent cytotoxicity (ADCC). However, there is a significant challenge due to the limited defucosylation efficiency of commercially available α-l-fucosidases. In this study, we report a unique α-l-fucosidase (PnfucA) from the bacterium Prevotella nigrescens that has a low sequence identity compared with all other known α-l-fucosidases and is highly reactive toward a core disaccharide substrate with fucose α(1,3)-, α (1,4)-and α(1,6)-linked to GlcNAc, and is less reactive toward the Fuc-α(1,2)-Gal on the terminal trisaccharide of the oligosaccharide Globo H (Bb3). The kinetic properties of the enzyme, such as its K_m and k_cat, were determined and the optimized expression of PnfucA gave a yield exceeding 30 mg/L. The recombinant enzyme retained its full activity even after being incubated for 6 h at 37 °C. Moreover, it retained 92 and 87% of its activity after freezing and freeze-drying treatments, respectively, for over 28 days. In a representative glycoengineering of adalimumab (Humira), PnfucA showed remarkable hydrolytic efficiency in cleaving the α(1,6)-linked core fucose from FucGlcNAc on the antibody with a quantitative yield. This enabled the seamless incorporation of biantennary sialylglycans by Endo-S2 D184 M in a one-pot fashion to yield adalimumab in a homogeneous afucosylated glycoform with an improved binding affinity toward Fcγ receptor IIIa.

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FUCA1

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