Structural significance of Neprylysin from Streptococcus suis GZ1 in the degradation of Aβ peptides, a causative agent in Alzheimer's disease

Kamble, Subodh A.; Barale, Sagar S.; Dhanavade, Maruti J.; Sonawane, Kailas D.

doi:10.1016/j.compbiomed.2021.104691

Cited by 8 publications

(16 citation statements)

References 62 publications

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“…These results were consistent with our report. In 2021, Kamble et al found that neprilysin enzyme from Streptococcus suis GZ1 can take part in cleave Aβ peptide [ 36 ]. This may explain the reduced abundance of Adlercreutzia in the Aβ-treated group.…”

Section: Discussionmentioning

confidence: 99%

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

Qian

Liu

Chen

et al. 2022

J Neuroinflammation

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Background Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD. Methods In this study, we constructed AD model mice by injecting Aβ1–42 into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group. Results Aβ1–42 i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ1–42 i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ1–42 treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ1–42 treatment group. Conclusions The present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.

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Section: Discussionmentioning

confidence: 99%

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

Qian

Liu

Chen

et al. 2022

J Neuroinflammation

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“…MD simulation has been successfully used to investigate molecular interactions and binding mode of several enzyme-ligand complexes (Dhanavade et al 2013 ; 2014 ; 2016 ; Sonawane and Barage 2015 ; Kamble et al 2021 ; Jalkute et al 2015b ; Ali et al 2023 ; Paymal et al 2023 ). The complexes CathD-C1, CathD-C2, CathD-C3 and CathD-C4 were selected for MD simulations as they expressed stable non-bonded interactions.…”

Section: Methodsmentioning

confidence: 99%

Structural insights into the potential binding sites of Cathepsin D using molecular modelling techniques

Kamble,

Barale,

Mohammed

et al. 2024

Amino Acids

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Alzheimer’s disease (AD) is the most prevalent type of dementia caused by the accumulation of amyloid beta (Aβ) peptides. The extracellular deposition of Aβ peptides in human AD brain causes neuronal death. Therefore, it has been found that Aβ peptide degradation is a possible therapeutic target for AD. CathD has been known to breakdown amyloid beta peptides. However, the structural role of CathD is not yet clear. Hence, for the purpose of gaining a deeper comprehension of the structure of CathD, the present computational investigation was performed using virtual screening technique to predict CathD's active site residues and substrate binding mode. Ligand-based virtual screening was implemented on small molecules from ZINC database against crystal structure of CathD. Further, molecular docking was utilised to investigate the binding mechanism of CathD with substrates and virtually screened inhibitors. Localised compounds obtained through screening performed by PyRx and AutoDock 4.2 with CathD receptor and the compounds having highest binding affinities were picked as; ZINC00601317, ZINC04214975 and ZINCC12500925 as our top choices. The hydrophobic residues Viz. Gly35, Val31, Thr34, Gly128, Ile124 and Ala13 help stabilising the CathD-ligand complexes, which in turn emphasises substrate and inhibitor selectivity. Further, MM-GBSA approach has been used to calculate binding free energy between CathD and selected compounds. Therefore, it would be beneficial to understand the active site pocket of CathD with the assistance of these discoveries. Thus, the present study would be helpful to identify active site pocket of CathD, which could be beneficial to develop novel therapeutic strategies for the AD.

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“…CRL's gene and AA sequences were extracted from the NCBI PDB [20]. An essential online server, the "SOPMA" program (Self-Optimized Prediction Method) (https: //npsa-pbil.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_sopma.html, accessed on 18 April 2023) [20,27], was utilized to analyze the secondary structure of the CRL sequence extracted from the National Center for Biotechnology Information (NCBI). This SOPMA analysis can give insight into the individual AAs involved in building the secondary structure with their positions [28].…”

Section: Secondary Structural Analysis and Homology Modeling Studies ...mentioning

confidence: 99%

“…The structure of CRL was extracted from RCSB [19]. After the completion of the secondary structure analysis, this extracted structure of CRL was further subjected to various online servers to assess its 3D structure and possible stereochemical quality using different analyses such as Protein Structure Analysis (ProSA) (https://prosa.services.came.sbg.ac.at/prosa.php, accessed on 18 April 2023), PROCHECK, VERIFY-3D [20], and ERRAT (https://saves.mbi.ucla.edu/, accessed on 18 April 2023) [29]. After the structure of the CRL was verified, it was employed for molecular docking analysis with the ZIF-8 ligand.…”

Section: Secondary Structural Analysis and Homology Modeling Studies ...mentioning

confidence: 99%

“…The ERRAT plot was employed to evaluate the mod and the AA environment. The protein is considered high quality when the estimated erro Upon analysis of CRL's extracted 3D structure using PROCHECK [20], it was observed that approximately 86.30% of residues were situated within the most favored regions, while 12.10% of residues were located in additional allowed regions. Additionally, 0.90% of residues were found to belong to generously allowed regions (Figure 2).…”

Section: Secondary Structural Analysis and Homology Modeling Studies ...mentioning

confidence: 99%

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Molecular Modeling Insights into Metal-Organic Frameworks (MOFs) as a Potential Matrix for Immobilization of Lipase: An In Silico Study

Patil

Kamble

Dhanavade

et al. 2023

Biology

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CRL is a highly versatile enzyme that finds extensive utility in numerous industries, which is attributed to its selectivity and catalytic efficiency, which have been impeded by the impracticality of its implementation, leading to a loss of native catalytic activity and non-reusability. Enzyme immobilization is a necessary step for enabling its reuse, and it provides methods for regulating the biocatalyst’s functional efficacy in a synthetic setting. MOFs represent a novel category of porous materials possessing distinct superlative features that make MOFs an optimal host matrix for developing enzyme-MOF composites. In this study, we employed molecular modeling approaches, for instance, molecular docking and MD simulation, to explore the interactions between CRL and a specific MOF, ZIF-8. The present study involved conducting secondary structural analysis and homology modeling of CRL, followed by docking ZIF-8 with CRL. The results of the molecular docking analysis indicate that ZIF-8 was situated within the active site pocket of CRL, where it formed hydrogen bonds with Val-81, Phe-87, Ser-91, Asp-231, Thr-132, Lue-297, Phe-296, Phe-344, Thr-347, and Ser-450. The MD simulation analysis revealed that the CRL and ZIF-8 docked complex exhibited stability over the entire simulation period, and all interactions presented in the initial docked complex were maintained throughout the simulation. The findings derived from this investigation could promote comprehension of the molecular mechanisms underlying the interaction between CRL and ZIF-8 as well as the development of immobilized CRL for diverse industrial purposes.

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Structural significance of Neprylysin from Streptococcus suis GZ1 in the degradation of Aβ peptides, a causative agent in Alzheimer's disease

Cited by 8 publications

References 62 publications

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer’s disease

Structural insights into the potential binding sites of Cathepsin D using molecular modelling techniques

Molecular Modeling Insights into Metal-Organic Frameworks (MOFs) as a Potential Matrix for Immobilization of Lipase: An In Silico Study

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