Molecular Basis for Recognition of the Cancer Glycobiomarker, LacdiNAc (GalNAc[β1→4]GlcNAc), by Wisteria floribunda Agglutinin*
Molecular Basis for Recognition of the Cancer Glycobiomarker, LacdiNAc (GalNAc[β1→4]GlcNAc), by Wisteria floribunda Agglutinin*
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紫藤凝集素识别癌症糖生物标志物 LacdiNAc (GalNAc[β1→4]GlcNAc) 的分子基础*
DOI：
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发表时间：
2016
影响因子：
4.8
通讯作者：
Stephen V. Evans
中科院分区：
文献类型：
--
作者：
O. Haji;M. Gilbert;J. Spence;M. Schur;Matthew J. Parker;M. Jenkins;John E. Burke;H. van Faassen;N. Young;Stephen V. Evans
异常糖基化和特定碳水化合物表位的过度表达是许多癌症的标志，并且肿瘤相关寡糖作为免疫治疗和诊断的靶标正在被积极研究。紫藤凝集素 (WFA) 是一种豆科植物凝集素，能够以高亲和力识别末端 N-乙酰氨基半乳糖。 WFA 优先结合二糖 LacdiNAc (β-d-GalNAc-[1→4]-d-GlcNAc)，其与白血病、前列腺癌、胰腺癌、卵巢癌和肝癌中的肿瘤恶性肿瘤相关，并在癌症糖生物标志物检测中显示出前景。 WFA 识别 LacdiNAc 的特异性机制尚不完全清楚。为了解决这个问题，我们确定了 WFA 与 GalNAc 和 LacdiNAc 复合物的亲和力和结构。通过表面等离子体共振测量对 Gal、GalNAc 和 LacdiNAc 的亲和力，得到的 KD 值分别为 4.67 × 10−4 m、9.24 × 10−5 m 和 5.45 × 10−6 m。 WFA 与 LacdiNAc 和 GalNAc 复合物的结构已确定为 1.80–2.32 Å 分辨率。这些高分辨率结构揭示了与 GalNAc 互补的疏水沟槽，并在较小程度上与 GlcNAc 糖环的背面互补。值得注意的是，这种小的疏水表面的贡献显着增加了观察到的 LacdiNAc 相对于 GalNAc 的亲和力。串联 MS 测序证实了市售 WFA 中存在两种异凝集素形式，仅在两个氨基酸的特性上有所不同。最后，WFA 碳水化合物结合位点类似于从 Vatairea macrocarpa 中分离出来的与 GalNAc 复合的同源凝集素，与 WFA 不同，它不仅结合 αGalNAc，还结合末端 Ser/Thr O 连接的 αGalNAc（Tn 抗原）。
Aberrant glycosylation and the overexpression of specific carbohydrate epitopes is a hallmark of many cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy and diagnostics. Wisteria floribunda agglutinin (WFA) is a legume lectin that recognizes terminal N-acetylgalactosaminides with high affinity. WFA preferentially binds the disaccharide LacdiNAc (β-d-GalNAc-[1→4]-d-GlcNAc), which is associated with tumor malignancy in leukemia, prostate, pancreatic, ovarian, and liver cancers and has shown promise in cancer glycobiomarker detection. The mechanism of specificity for WFA recognition of LacdiNAc is not fully understood. To address this problem, we have determined affinities and structure of WFA in complex with GalNAc and LacdiNAc. Affinities toward Gal, GalNAc, and LacdiNAc were measured via surface plasmon resonance, yielding KD values of 4.67 × 10−4 m, 9.24 × 10−5 m, and 5.45 × 10−6 m, respectively. Structures of WFA in complex with LacdiNAc and GalNAc have been determined to 1.80–2.32 Å resolution. These high resolution structures revealed a hydrophobic groove complementary to the GalNAc and, to a minor extent, to the back-face of the GlcNAc sugar ring. Remarkably, the contribution of this small hydrophobic surface significantly increases the observed affinity for LacdiNAc over GalNAc. Tandem MS sequencing confirmed the presence of two isolectin forms in commercially available WFA differing only in the identities of two amino acids. Finally, the WFA carbohydrate binding site is similar to a homologous lectin isolated from Vatairea macrocarpa in complex with GalNAc, which, unlike WFA, binds not only αGalNAc but also terminal Ser/Thr O-linked αGalNAc (Tn antigen).
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曼氏血吸虫提取物中新型 UDPGalNAc:GlcNAc beta 1-4 N-乙酰半乳糖胺基转移酶的演示。
DOI：
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发表时间：
1994
期刊：
The Journal of parasitology
影响因子：
--
作者：
Srivatsan,J;Smith,DF;Cummings,RD
通讯作者：
Cummings,RD
影响因子：
4.3
作者：
Bojarova, Pavla;Krenek, Karel;Kren, Vladimir
通讯作者：
Kren, Vladimir
曼氏血吸虫成年雄性合成的糖蛋白中的复合型天冬酰胺连接寡糖含有末端β连接的N-乙酰半乳糖胺。
DOI：
--
发表时间：
1989
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Nyame,K;Smith,DF;Damian,RT;Cummings,RD
通讯作者：
Cummings,RD
影响因子：
6.8
作者：
Karplus PA;Diederichs K
通讯作者：
Diederichs K