更新于：2024-11-01

MAN2A1

更新于：2024-11-01

基本信息

别名

Alpha-mannosidase 2、AMan II、Golgi alpha-mannosidase II

+ [8]

简介

Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.

关联

项与 MAN2A1 相关的药物

Swainsonine hydrochloride

靶点

MAN2A1

作用机制

MAN2A1抑制剂

在研机构-

原研机构

Orexo AB

在研适应症-

非在研适应症

化疗引起的损伤 [+6]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

Swainsonine

靶点

MAN2A1

作用机制

MAN2A1抑制剂 [+3]

在研机构-

原研机构

Astellas Pharma, Inc.

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MAN2A1 相关的临床结果

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100 项与 MAN2A1 相关的转化医学

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0 项与 MAN2A1 相关的专利（医药）

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822

项与 MAN2A1 相关的文献（医药）

2024-11-01·Journal of Allergy and Clinical Immunology: Global

Agaricus bisporus mushroom anaphylaxis: A case report and review of the literature

Article

作者: Ali, Syed B ; Smith, William ; Ali, Syed B.

BackgroundAnaphylaxis in response to edible mushrooms is uncommon, and sensitization may be independent of occupational exposure. Globally, A garicus bisporus is one the most cultivated mushroom species, comprising the button, portobello, and Swiss brown varietals.ObjectiveOur aim was to describe a case of anaphylaxis in an older nonatopic patient following ingestion of A bisporus and undertake a review of the literature.MethodsA 77-year-old female was referred to the allergy clinic with a history of grade 3 hypotensive anaphylaxis following ingestion of a mushroom omelette. Her tryptase level 4 hours following acute symptoms was elevated. She continued to consume all other omelette ingredients with the exception of mushroom. Additional investigations included specific IgE testing as well as comprehensive skin prick testing (SPT) to raw and boiled mushrooms.ResultsOne month after her index reaction, the result of SPT to boiled button mushroom was positive. The patient's baseline tryptase level was normal. The results of further SPT with other commonly available boiled mushrooms (the A bisporus mushrooms portobello and Swiss brown, as well as enoki, oyster, and shiitake mushrooms) were also positive.A review of the literature revealed 27 other cases, with an average patient age of 28.8 years (range 8-68 years) and no gender predisposition. Cases from Europe (n = 14, 51.8%) and Asia (n = 12, 44.4%) comprised the majority of the reports. A bisporus was reported in more than one-third of the cases (n = 10, 37.1%) from Australia, India, Portugal, Spain, and the United Kingdom. Cross-sensitization among the edible mushroom species was evident for those individuals who were tested, but no clear and consistent pattern was identified. In some cases, further diagnostics identified α-mannosidase, α-trehalose, mannitol, and ribosomal protein as specific mushroom allergens.ConclusionClinicians should be aware of mushroom as a cause for anaphylaxis, especially in nonatopic and de novo presentations.

2024-09-01·Bioorganic Chemistry

(5S)-5-Benzylswainsonines as potent and selective inhibitors of Golgi α-mannosidase II: synthesis, enzyme evaluation and molecular modelling

Article

作者: Moncoľ, Ján ; Kalník, Martin ; Kóňa, Juraj ; Šesták, Sergej ; Bella, Maroš ; Gabko, Peter

Development of novel anti-cancer therapeutics based on Golgi α-mannosidase II (GMII) inhibition is considerably impeded by an undesired co-inhibition of lysosomal α-mannosidase leading to severe side-effects. In this contribution, we describe a fully stereoselective synthesis of (5S)-5-[4-(halo)benzyl]swainsonines as highly potent and selective inhibitors of GMII. The synthesis starts from a previously reported aldehyde readily available from l-ribose, and the key features include an intramolecular reductive amination with substrate-controlled stereoselectivity and a late-stage derivatisation of the benzyl group via ipso-substitution. These novel swainsonine analogues were found to be nanomolar inhibitors of the Golgi-type α-mannosidase AMAN-2 (K_i = 23-75 nM) with excellent selectivity (selectivity index = 205-870) over the lysosomal-type Jack bean α-mannosidase. Finally, molecular docking and pK_a calculations were performed to provide more insight into the structure of the inhibitor:enzyme complexes, and a pair interaction energy analysis (FMO-PIEDA) was carried out to rationalise the observed potency and selectivity of the inhibitors.

2024-09-01·Gut

Lactococcus lactis HkyuLL 10 suppresses colorectal tumourigenesis and restores gut microbiota through its generated alpha-mannosidase

Article

作者: Ding, Yanqiang ; Jiang, Lanping ; Yu, Jun ; Kang, Xing ; Cheung, Alvin Ho-Kwan ; To, Ka Fai ; Lau, Harry Cheuk Hay ; Wang, Xueliang ; Liu, Yali ; Lu, Yinghong ; Liu, Weixin ; Ding, Xiao ; Su, Anthony Chin Yang ; Li, Qing

Objective Probiotic Lactococcus lactis is known to confer health benefits to humans. Here, we aimed to investigate the role of L. lactis in colorectal cancer (CRC). DesignL. lactis abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536). L. lactis was isolated from healthy human stools with verification by whole genome sequencing. The effect of L. lactis on CRC tumourigenesis was assessed in transgenic ApcMin/+ mice and carcinogen-induced CRC mice. Faecal microbiota was profiled by metagenomic sequencing. Candidate proteins were characterised by nano liquid chromatography-mass spectrometry. Biological function of L. lactis conditioned medium ( HkyuLL 10 -CM) and functional protein was studied in human CRC cells, patient-derived organoids and xenograft mice. Results Faecal L. lactis was depleted in patients with CRC. A new L. lactis strain was isolated from human stools and nomenclated as HkyuLL 10. HkyuLL 10 supplementation suppressed CRC tumourigenesis in ApcMin/+ mice, and this tumour-suppressing effect was confirmed in mice with carcinogen-induced CRC. Microbiota profiling revealed probiotic enrichment including Lactobacillus johnsonii in HkyuLL 10 -treated mice. HkyuLL 10 -CM significantly abrogated the growth of human CRC cells and patient-derived organoids. Such protective effect was attributed to HkyuLL 10 -secreted proteins, and we identified that α-mannosidase was the functional protein. The antitumourigenic effect of α-mannosidase was demonstrated in human CRC cells and organoids, and its supplementation significantly reduced tumour growth in xenograft mice. ConclusionHkyuLL 10 suppresses CRC tumourigenesis in mice through restoring gut microbiota and secreting functional protein α-mannosidase. HkyuLL 10 administration may serve as a prophylactic measure against CRC.