Structural and enzymatic characterization of the sialidase SiaPG from Porphyromonas gingivalis

IF 1.1 4区 生物学 Q4 BIOCHEMICAL RESEARCH METHODS Acta crystallographica. Section F, Structural biology communications Pub Date : 2023-03-30 DOI:10.1107/S2053230X23001735
Wen-Bo Dong, Yong-Liang Jiang, Zhong-Liang Zhu, Jie Zhu, Yang Li, Rong Xia, Kang Zhou
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引用次数: 1

Abstract

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 Å 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.

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牙龈卟啉单胞菌唾液酸酶SiaPG的结构和酶学表征
唾液酸酶是多种致病菌的一组主要毒力因子,它能催化胞外糖缀合物水解唾液酸。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胶囊的形成、降低巨噬细胞的清除能力和为细菌定植提供营养物质来促进细菌的发病。本文以2.1 Å的分辨率报道了牙龈卟啉唾液酸酶SiaPG的晶体结构,揭示了一个n端碳水化合物结合结构域,然后是一个典型的c端催化结构域。活性位点口袋中唾液酸产物的模拟以及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位点口袋的独特特征,这可能赋予底物特异性。这些发现为进一步设计和优化有效的SiaPG抑制剂来对抗牙龈卟啉卟啉衍生的口腔疾病提供了结构基础。
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来源期刊
Acta crystallographica. Section F, Structural biology communications
Acta crystallographica. Section F, Structural biology communications BIOCHEMICAL RESEARCH METHODSBIOCHEMISTRY &-BIOCHEMISTRY & MOLECULAR BIOLOGY
CiteScore
1.90
自引率
0.00%
发文量
95
期刊介绍: Acta Crystallographica Section F is a rapid structural biology communications journal. Articles on any aspect of structural biology, including structures determined using high-throughput methods or from iterative studies such as those used in the pharmaceutical industry, are welcomed by the journal. The journal offers the option of open access, and all communications benefit from unlimited free use of colour illustrations and no page charges. Authors are encouraged to submit multimedia content for publication with their articles. Acta Cryst. F has a dedicated online tool called publBio that is designed to make the preparation and submission of articles easier for authors.
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