共同群中的多样性:对格兰氏阴性病原体的D类β-乳糖酶的结构洞察
Clyde A Smith1,2, Anastasiya Stasyuk1,3
1Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
Pathogens (Basel, Switzerland)
|August 28, 2025
概括
D类β-乳酸酶 (DBLs) 通过降解卡巴类药物来威胁抗生素的有效性. 它们的B环与P环和 Ω环一起,极大地影响了Gram阴性细菌中的酶活性和碳酶功能.
科学领域:
- 微生物学
- 结构生物学
- 生物化学
背景情况:
- D类β-乳酸酶 (DBLs) 是格拉姆阴性细菌抗菌性的主要驱动因素.
- DBLs能使β- 乳酸抗生素,包括卡巴胺,无效.
- 这些酶具有保留的α/β结构,具有活性位点的动图和灵活的循环 (P-循环, Ω-循环, B-循环).
研究的目的:
- 研究P环, Ω环和B环在DBL函数中的协调作用.
- 在临床上相关的DBL中阐明这些循环的结构和动态相互作用.
- 了解循环结构如何影响碳酶活动和基质识别.
主要方法:
- 对40个DBL进行比较序列和晶体结构分析.
- 在选择的DBL代表的分子动力学模拟.
- 对B环结构与碳酶活性的相关性分析.
主要成果:
- 在Klebsiella和Acinetobacter中的B环结构 (长度,空间组织) 和碳酶活性之间观察到强烈的相关性.
- B-循环,P-循环和 Ω-循环协同工作以调节主动站点的多功能性.
- 这些循环对于基质识别,催化活性和酶结构稳定性至关重要.
结论:
- 在确定 DBL 功能和碳酶活性方面,B 循环与 P 循环和 Ω 循环一起发挥关键作用.
- 了解循环相互作用可以了解抗菌素耐药性机制.
- 这种知识可以指导新型抗生素和DBL抑制剂的开发.
相关概念视频
Bacterial Cell Wall
579
The bacterial cell wall is an essential structural component that encases the plasma membrane, preserving cellular integrity, determining shape, and protecting against osmotic stress. This rigid yet flexible structure primarily comprises peptidoglycan, a polymer that forms a mesh-like matrix conferring mechanical strength and flexibility.Peptidoglycan Composition and StructurePeptidoglycan, the core of the bacterial cell wall, comprises alternating units of N-acetylglucosamine (NAG) and...
579
Development of Antibiotic Resistance
197
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
197
Methods of Classification and Identification
183
Bacterial identification relies on a diverse array of techniques to classify and understand microorganisms, each tailored to uncover specific characteristics. Traditional morphological approaches, while still valuable, are limited for closely related or structurally simple organisms. Modern methods integrate biochemical, serological, genetic, and advanced molecular tools to achieve greater accuracy.Morphological and Biochemical TechniquesMorphological characteristics, such as cell shape and...
183
Gram-negative Bacterial Protein Secretion Systems
148
Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
148
Gene Regulation in Microbial Communities: Quorum Sensing
92
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
92
Bacterial Phylum Proteobacteria
131
Proteobacteria, one of the largest and most diverse bacterial phyla, encompasses a wide range of Gram-negative bacteria distinguished by their outer membrane composed of lipopolysaccharides. These microorganisms exhibit various metabolic capabilities, including phototrophy, chemolithotrophy, and heterotrophy, and thrive in diverse environments from soil to aquatic systems and host-associated niches. The phylum is divided into six classes: Alphaproteobacteria, Betaproteobacteria,...
131


