Trp358 is a key residue for the multiple catalytic activities of multifunctional amylase OPMA-N from Bacillus sp. ZW2531-1

Cao, Hao; Gao, Gui; Gu, Yanqin; Zhang, Jinxiang; Zhang, Yingjiu

doi:10.1007/s00253-013-5085-5

Cited by 13 publications

(1 citation statement)

References 31 publications

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“…The 3D structure of the selected scFv was built via the Insight II/ Builder program. The molecular docking of Aβ42 to the selected scFv was carried out using the program AutoDock 4.0 as described previously [26,27]. The structural integrities of the models were visually examined by Discovery Studio (DS) Visualizer 3.1 (http://accelrys.com/products/discoverystudio/visualization-download.php).…”

Section: Molecular Dockingmentioning

confidence: 99%

Functional Characteristics and Molecular Mechanism of a New scFv Antibody Against Aβ42 Oligomers and Immature Protofibrils

et al. 2014

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Amyloid β peptide (Aβ42) is a major determinant of Alzheimer's disease (AD). In this study, we studied a novel single-chain variable fragment (scFv), AS, generated from an antibody library of AD patients, which recognized and bound specifically to medium-size amyloid β peptide (Aβ42) oligomers and immature protofibrils (25-55 kDa) and, more importantly, reduced their level by blocking their formation or inducing their disassembly. Consequently, scFv AS ameliorated or prevented their cytotoxicity and protected SH-SY5Y cells and primary cultured neurons in vitro from their damage in a concentration-dependent manner. Comparison of its cytotoxicity-inhibiting and cytotoxicity-neutralizing activities indicated that scFv AS displayed its protective effect on target cells mainly due to its cytotoxicity-inhibitory activity though it could also neutralize the cytotoxicity. We also found that scFv AS could efficiently cross the in vitro BBB model with a delivery efficiency of over 70% after a 60-min post-administration. The scFv AS was a monovalent antibody with an affinity constant (KD) of 5.5 × 10(-6) M and a binding threshold of 6.25 × 10(-4) μM for Aβ42 oligomers. The molecular docking simulations of Aβ42 to scFv AS revealed that scFv AS tends to approached Aβ42 oligomers and immature protofibrils mainly by their hydrophobic interaction and then drew Aβ42 molecule into the gap between VL and VH domains of scFv AS by hydrophilic interaction between scFv AS and the N-terminal region (residues 1-15) of Aβ42 and the hydrophobic interactions between scFv AS and the middle region (residues 20-33) of Aβ42. The combination of scFv AS with Aβ42 was realized likely through an induced-fit process.

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Section: Molecular Dockingmentioning

confidence: 99%

Functional Characteristics and Molecular Mechanism of a New scFv Antibody Against Aβ42 Oligomers and Immature Protofibrils

et al. 2014

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The second conserved motif in bacterial laccase regulates catalysis and robustness

Jin

Yang

Sheng

et al. 2018

Appl Microbiol Biotechnol

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Laccase (EC1.10.3.2), an oxidase that binds multiple copper ions, is heterogeneous in different species, implying diversity in its function. Nevertheless, the four copper-binding motifs are conserved in most laccases, especially bacterial forms. In order to exploit laccase more widely and more effectively in industrial processes, we investigated the regulatory effects, if any, of the second conserved copper-binding motif in the bacterial laccases CAR2 and CAHH1. The data suggested that three critical amino acid residues His155, His157, and Thr/Ala158 in this motif strongly regulated laccase's catalysis, substrate range, and robustness. Indeed, these residues were essential for laccase's catalytic activity. The data also suggested that laccase's catalytic efficiency and activity are not completely consistent with its stability, and that the enzyme might have evolved naturally to its favor stability. This study provides important insights into the second conserved copper-binding motif and defines some of the previously undefined amino acid residues in this conserved motif and their significances.

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A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer’s Disease Transgenic Mice by Inhibiting Aβ Aggregation and Blocking the RAGE/Aβ Axis

et al. 2016

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The treatment of AD is a topic that has puzzled researchers for many years. Current mainstream theories still consider Aβ to be the most important target for the cure of AD. In this study, we attempted to explore multiple targets for AD treatments with the aim of identifying a qualified compound that could both inhibit the aggregation of Aβ and block the RAGE/Aβ axis. We believed that a compound that targets both Aβ and RAGE may be a feasible strategy for AD treatment. A novel and small natural compound, Matrine (Mat), was identified by high-throughput screening of the main components of traditional Chinese herbs used to treat dementia. Various experimental techniques were used to evaluate the effect of Mat on these two targets both in vitro and in AD mouse model. Mat could inhibit Aβ42-induced cytotoxicity and suppress the Aβ/RAGE signaling pathway in vitro. Additionally, the results of in vivo evaluations of the effects of Mat on the two targets were consistent with the results of our in vitro studies. Furthermore, Mat reduced proinflammatory cytokines and Aβ deposition and attenuated the memory deficits of AD transgenic mice. We believe that this novel, multi-target strategy to inhibit both Aβ and RAGE, is worthy of further exploration. Therefore, our future studies will focus on identifying even more effective multi-target compounds for the treatment of AD based on the molecular structure of Mat.

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Trp358 is a key residue for the multiple catalytic activities of multifunctional amylase OPMA-N from Bacillus sp. ZW2531-1

Cited by 13 publications

References 31 publications

Functional Characteristics and Molecular Mechanism of a New scFv Antibody Against Aβ42 Oligomers and Immature Protofibrils

Functional Characteristics and Molecular Mechanism of a New scFv Antibody Against Aβ42 Oligomers and Immature Protofibrils

The second conserved motif in bacterial laccase regulates catalysis and robustness

A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer’s Disease Transgenic Mice by Inhibiting Aβ Aggregation and Blocking the RAGE/Aβ Axis

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