Structural and enzymatic characterization of the sialidase SiaPG from Porphyromonas gingivalis
Structural and enzymatic characterization of the sialidase SiaPG from Porphyromonas gingivalis
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DOI：
10.1107/s2053230x23001735
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发表时间：
2023-04-01
影响因子：
0.9
通讯作者：
Zhou, Kang
中科院分区：
文献类型：
--
作者：
Dong, Wen-Bo;Jiang, Yong-Liang;Zhou, Kang
唾液酸酶是多种致病菌中的一组主要毒力因子，催化胞外糖偶联物中唾液酸的水解。在引起人类牙周病的牙龈卟啉单胞菌中，唾液酸酶通过促进生物膜和包膜的形成，降低巨噬细胞的清除能力，为细菌定植提供营养，从而参与细菌的发病。在这里，报道了牙龈假单胞菌唾液酸酶SiaPG的晶体结构，分辨率为2.1埃，揭示了一个N-末端的碳水化合物结合结构域和一个典型的C-末端催化结构域。模拟活性部位口袋中的产物唾液酸，结合功能分析，可以清楚地识别底物结合和催化所需的关键残基。此外，与其他唾液酸酶的结构比较揭示了活性部位口袋的明显特征，这可能赋予底物专一性。这些发现为进一步设计和优化针对SiaPG的有效抑制剂以对抗牙龈假单胞菌衍生的口腔疾病提供了结构基础。
The sialidases, which catalyze the hydrolysis of sialic acid from extracellular glycoconjugates, are a group of major virulence factors in various pathogenic bacteria. In Porphyromonas gingivalis, which causes human periodontal disease, sialidase contributes to bacterial pathogenesis via promoting the formation of biofilms and capsules, reducing the ability for macrophage clearance, and providing nutrients for bacterial colonization. Here, the crystal structure of the P. gingivalis sialidase SiaPG is reported at 2.1 angstrom resolution, revealing an N-terminal carbohydrate-binding domain followed by a canonical C-terminal catalytic domain. Simulation of the product sialic acid in the active-site pocket together with functional analysis enables clear identification of the key residues that are required for substrate binding and catalysis. Moreover, structural comparison with other sialidases reveals distinct features of the active-site pocket which might confer substrate specificity. These findings provide the structural basis for the further design and optimization of effective inhibitors to target SiaPG to fight against P. gingivalis-derived oral diseases.