Action pattern and substrate specificity of the hyaluronan lyase from group B streptococci
Action pattern and substrate specificity of the hyaluronan lyase from group B streptococci
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DOI：
10.1042/0264-6021:3480465
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发表时间：
2000-06-01
影响因子：
4.1
通讯作者：
Pritchard, DG
中科院分区：
文献类型：
--
作者：
Baker, JR;Pritchard, DG
B 族链球菌的透明质酸裂解酶通过消除机制快速裂解透明质酸，产生不饱和二糖 2-乙酰氨基-2-脱氧-3-O-(β-D-葡萄糖-4-烯吡喃糖醛酸)-D-葡萄糖。此外，已表明该酶对硫酸软骨素的特异性有限，并在非硫酸化位点裂解链[Baker, Yu, Morrison, Averett 和 Pritchard (1997) Biochem. J，327，65-71]。在该研究的当前扩展中，发现硫酸软骨素的 6-硫酸化区域也容易被这种乙酰透明质酸裂解酶裂解。在可以从硫酸软骨素的睾丸透明质酸酶消化物中分离出的四种6-和/或4-硫酸化四糖中，只有那两种在还原端具有6-硫酸化二糖的四糖被裂解。根据该数据和其他数据，提出了透明质酸裂解酶对硫酸软骨素的裂解特异性的模型。有证据支持透明质酸裂解酶的作用模式，该模式涉及初始随机内溶裂解，随后是不饱和二糖的快速外切和持续释放。由于在透明质酸的接近完全消化物中倾向于积累的唯一寡糖是不饱和的，因此认为持续裂解发生在透明质酸链的非还原端至还原端。对底物特异性的详细了解有助于我们了解该酶在 B 组链球菌发病机制中的作用。此外，透明质酸裂解酶还可用于硫酸软骨素的序列研究。
The hyaluronan lyase of group B streptococci rapidly cleaves hyaluronan by an elimination mechanism to yield the unsaturated disaccharide 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyrano- syluronic acid)-D-glucose. Additionally, it has been shown that the enzyme has limited specificity for a chondroitin sulphate and cleaves the chain at unsulphated sites [Baker, Yu, Morrison, Averett and Pritchard (1997) Biochem. J, 327, 65-71]. In the present extension of that study it was found that 6-sulphated regions of chondroitin sulphate are also susceptible to cleavage by this hyaluronan lyase. Of the four 6- and/or 4-sulphated tetrasaccharides which can be isolated from testicular hyaluronidase digests of chondroitin sulphate, only those two tetrasaccharides with a 6-sulphated disaccharide at the reducing end were cleaved. From this and other data, a model is proposed for the cleavage specificity of hyaluronan lyase on a chondroitin sulphate. Evidence is presented in support of an action pattern for hyaluronan lyase which involves an initial random endolytic cleavage followed by rapid exolytic and processive release of unsaturated disaccharide. Since the only oligosaccharides which tend to accumulate in near-complete digests of hyaluronan are unsaturated, it is argued that the processive cleavage occurs from the non-reducing to the reducing end of a hyaluroman chain. This detailed knowledge of substrate specificity contributes to our understanding of the enzyme's role in Group B streptococcal pathogenesis. In addition, the hyaluronan lyase may find application in sequence studies of chondroitin sulphates.