Functional characterization of a 3-O-sulfate tolerant heparin lyase from Bacteroides eggerthii.

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Glycobiology Pub Date : 2026-09-29 DOI:10.1093/glycob/cwag097

Taran K Kandola, Courtney J Mycroft-West, Marcelo A Lima, Abigail Turner, Cristina Gardini, Elena Urso, Thomas A Torode, Gavin J Miller, Antonella Bisio, Edwin A Yates, Marco Guerrini, Mark A Skidmore, Liang Wu

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引用次数: 0

Abstract

Heparin is a sulfated glycosaminoglycan, and the most used pharmaceutical anticoagulant worldwide. Heparin is isolated primarily from porcine sources, and possesses a complex variable structure, wherein anticoagulant activity is principally derived from the pentasaccharide GlcNS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA) motif, containing an infrequent 3-O-sulfated glucosamine that enhances antithrombin stabilization. Pedobacter heparinus heparin lyases are currently widely employed for characterization of heparin and its derivatives, but have limited activity near regions of 3-O-sulfation, hindering analyses of anticoagulation relevant sequences. Here, using a panel of biophysical and structural techniques, we show that Bacteroides eggerthii lyase I liberates ΔUA-GlcNS3S6S disaccharides from the defined pentasaccharide, fondaparinux. This activity provides improved access to 3-O-sulfated heparin standards, with potential to aid heparin quality control.

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蛋拟杆菌中3- o -硫酸盐耐受性肝素裂解酶的功能表征。

肝素是一种磺化糖胺聚糖，是世界上使用最广泛的抗凝药物。肝素主要从猪源中分离出来，具有复杂的可变结构，其中抗凝血活性主要来源于五糖GlcNS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S （AGA*IA）基序，包含罕见的3- o -硫酸氨基葡萄糖，增强抗凝血酶稳定性。Pedobacter heparinus肝素裂解酶目前广泛用于肝素及其衍生物的表征，但在3- o -硫酸化区域附近的活性有限，阻碍了抗凝相关序列的分析。在这里，使用一组生物物理和结构技术，我们表明拟杆菌卵磷脂裂解酶I从定义的五糖，fondaparinux中释放ΔUA-GlcNS3S6S双糖。这一活动改善了获得3- o -硫代肝素标准的途径，有可能有助于肝素质量控制。

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来源期刊

Glycobiology 生物-生化与分子生物学

CiteScore

7.50

自引率

4.70%

发文量

审稿时长

3 months

期刊介绍： Established as the leading journal in the field, Glycobiology provides a unique forum dedicated to research into the biological functions of glycans, including glycoproteins, glycolipids, proteoglycans and free oligosaccharides, and on proteins that specifically interact with glycans (including lectins, glycosyltransferases, and glycosidases). Glycobiology is essential reading for researchers in biomedicine, basic science, and the biotechnology industries. By providing a single forum, the journal aims to improve communication between glycobiologists working in different disciplines and to increase the overall visibility of the field.