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Publications (10 of 60) Show all publications
Fu, Y., Kang, Z., Yin, J., Cao, W., Tu, Y., Wang, Q. & Kong, X. (2019). Duet of Acetate and Water at the Defects of Metal-Organic Frameworks. Nano letters (Print), 19(3), 1618-1624
Open this publication in new window or tab >>Duet of Acetate and Water at the Defects of Metal-Organic Frameworks
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2019 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 19, no 3, p. 1618-1624Article in journal (Refereed) Published
Abstract [en]

Metal-organic frameworks (MOFs) are porous crystalline materials with promising applications in molecular adsorption, separation, and catalysis. It has been discovered recently that structural defects introduced unintentionally or by design could have a significant impact on their properties. However, the exact chemical composition and structural evolution under different conditions at the defects are still under debate. In this study, we performed multidimensional solid-state nuclear magnetic resonance (SSNMR) coupled with computer simulations to elucidate an important scenario of MOF defects, uncovering the dynamic interplay between residual acetate and water. Acetate, as a defect modulator, and water, as a byproduct, are prevalent defect-associated species, which are among the key factors determining the reactivity and stability of defects. We discovered that acetate molecules coordinate to a single metal site monodentately and pair with water at the neighboring position. The acetates are highly flexible, which undergo fast libration as well as a slow kinetic exchange with water through dynamic hydrogen bonds. The dynamic processes under variable temperatures and different hydration levels have been quantitatively analyzed across a broad time scale from microseconds to seconds. The integration of SSNMR and computer simulations allows a precision probe into defective MOF structures with intrinsic dynamics and disorder.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
Metal-organic frameworks, defects, dynamics, solid-state NMR, molecular dynamics simulations
National Category
Other Chemistry Topics
Identifiers
urn:nbn:se:kth:diva-248355 (URN)10.1021/acs.nanolett.8b04518 (DOI)000461537600026 ()30716273 (PubMedID)2-s2.0-85061544832 (Scopus ID)
Note

QC 20190405

Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-05Bibliographically approved
Zou, R., Guanglin, K., Ågren, H., Nordberg, A., Långström, B. & Tu, Y. (2019). Free Energy Profile for Penetration of Pittsburgh Compound-B into the Amyloid beta Fibril. ACS Chemical Neuroscience, 10(3), 1783-1790
Open this publication in new window or tab >>Free Energy Profile for Penetration of Pittsburgh Compound-B into the Amyloid beta Fibril
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2019 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 3, p. 1783-1790Article in journal (Refereed) Published
Abstract [en]

The amyloid beta (A beta) fibril is a hallmark of Alzheimer's disease (AD) and has therefore served as an important target for early diagnosis of AD. The Pittsburgh Compound-B (PiB) is one of the most famous positron emission tomography (PET) tracers commonly used for in vivo detection of A beta fibrils. Many theoretical studies have predicted the existence of various core binding sites with different microenvironments for probes binding to the A beta fibril. However, little attention has been devoted to how the probes actually penetrate into the different core binding sites. In this study, an integrated molecular modeling scheme is used to study the penetration of PiB into the core binding sites of the A beta(1-42) fibril structure recently obtained by cryogenic electron microscopy. We find that there are two core binding sites for PiB with dramatic differences in cavity size and microenvironment properties, and furthermore that the penetration of PiB into site-1 is energetically prohibitive, whereas the penetration into site 2 is much more favorable. Therefore, the binding capacity at site-2 may be larger than that at site-1 despite its lower binding affinity. Our results thus suggest that site-2 may be a major binding site for PiB binding to A beta fibril and emphasize the importance to adopt a full dynamical picture when studying tracer fibril binding problems in general, something that in turn can be used to guide the development of tracers with higher affinity and selectivity for the A beta fibril.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
Amyloid beta fibril, binding sites, imaging agents, free energy profiles, molecular dynamics simulation, umbrella sampling
National Category
Neurosciences
Identifiers
urn:nbn:se:kth:diva-249893 (URN)10.1021/acschemneuro.8b00662 (DOI)000462259900081 ()30698013 (PubMedID)2-s2.0-85061903405 (Scopus ID)
Note

QC 20190424

Available from: 2019-04-24 Created: 2019-04-24 Last updated: 2019-05-10Bibliographically approved
Zou, R., Zhu, X., Tu, Y., Wu, J. & Landry, M. P. (2018). Activity of Antimicrobial Peptide Aggregates Decreases with Increased Cell Membrane Embedding Free Energy Cost. Biochemistry, 57(18), 2606-2610
Open this publication in new window or tab >>Activity of Antimicrobial Peptide Aggregates Decreases with Increased Cell Membrane Embedding Free Energy Cost
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2018 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 57, no 18, p. 2606-2610Article in journal (Refereed) Published
Abstract [en]

Antimicrobial peptides (AMPs) are a promising alternative to antibiotics for mitigating bacterial infections, in light of increasing bacterial resistance to antibiotics. However, predicting, understanding, and controlling the antibacterial activity of AMPs remain a significant challenge. While peptide intramolecular interactions are known to modulate AMP antimicrobial activity, peptide intermolecular interactions remain elusive in their impact on peptide bioactivity. Herein, we test the relationship between AMP intermolecular interactions and antibacterial efficacy by controlling AMP intermolecular hydrophobic and hydrogen bonding interactions. Molecular dynamics simulations and Gibbs free energy calculations in concert with experimental assays show that increasing intermolecular interactions via interpeptide aggregation increases the energy cost for the peptide to embed into the bacterial cell membrane, which in turn decreases the AMP antibacterial activity. Our findings provide a route for predicting and controlling the antibacterial activity of AMPs against Gram-negative bacteria via reductions of intermolecular AMP interactions.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Biophysics
Identifiers
urn:nbn:se:kth:diva-228427 (URN)10.1021/acs.biochem.8b00052 (DOI)000431927100008 ()29638118 (PubMedID)2-s2.0-85046780456 (Scopus ID)
Note

QC 20180529

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2019-05-10Bibliographically approved
Li, J., Zhang, H., Liu, G., Tang, Y., Tu, Y. & Li, W. (2018). Computational Insight Into Vitamin K-1 omega-Hydroxylation by Cytochrome P450 4F2. Frontiers in Pharmacology, 9, Article ID 1065.
Open this publication in new window or tab >>Computational Insight Into Vitamin K-1 omega-Hydroxylation by Cytochrome P450 4F2
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2018 (English)In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 9, article id 1065Article in journal (Refereed) Published
Abstract [en]

Vitamin K-1 (VK1) plays an important role in the modulation of bleeding disorders. It has been reported that omega-hydroxylation on the VK1 aliphatic chain is catalyzed by cytochrome P450 4F2 (CYP4F2), an enzyme responsible for the metabolism of eicosanoids. However, the mechanism of VK1 omega-hydroxylation by CYP4F2 has not been disclosed. In this study, we employed a combination of quantum mechanism (QM) calculations, homology modeling, molecular docking, molecular dynamics (MD) simulations, and combined quantum mechanism/molecular mechanism (QM/MM) calculations to investigate the metabolism profile of VK1 omega-hydroxylation. QM calculations based on the truncated VK1 model show that the energy barrier for omega-hydroxylation is about 6-25 kJ/mol higher than those at other potential sites of metabolism. However, results from the MD simulations indicate that hydroxylation at the omega-site is more favorable than at the other potential sites, which is in accordance with the experimental observation. The evaluation of MD simulations was further endorsed by the QM/MM calculation results. Our studies thus suggest that the active site residues of CYP4F2 play a determinant role in the omega-hydroxylation. Our results provide structural insights into the mechanism of VK1 omega-hydroxylation by CYP4F2 at the atomistic level and are helpful not only for characterizing the CYP4F2 functions but also for looking into the omega-hydroxylation mediated by other CYP4 enzymes.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
cytochrome P450, CYP4F2, omega-hydroxylation, molecular dynamics, QM/MM, homology modeling, vitamin K-1
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-235873 (URN)10.3389/fphar.2018.01065 (DOI)000445589400001 ()2-s2.0-8502-s2.0-8505514567155145671 (Scopus ID)
Note

QC 20181009

Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2019-05-07Bibliographically approved
Zhao, X., Li, R., Zhou, Y., Xiao, M., Ma, C., Yang, Z., . . . Hu, W. (2018). Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses. Journal of Medicinal Chemistry, 61(12), 5187-5198
Open this publication in new window or tab >>Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses
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2018 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, no 12, p. 5187-5198Article in journal (Refereed) Published
Abstract [en]

Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure-activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor M090 against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that M090 targets influenza HA and it occupied a highly conserved pocket of the HA(2) domain and inhibited virus-mediated membrane fusion by "locking" the bending state of HA(2) during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:kth:diva-232630 (URN)10.1021/acs.jmedchem.8b00042 (DOI)000437811200009 ()29799746 (PubMedID)2-s2.0-85047723145 (Scopus ID)
Funder
Swedish National Infrastructure for Computing (SNIC)
Note

QC 20180730

Available from: 2018-07-30 Created: 2018-07-30 Last updated: 2018-07-30Bibliographically approved
Zhou, Y., Hussain, M., Guanglin, K., Zhang, J. & Tu, Y. (2018). Mechanistic insights into peptide and ligand binding of the ATAD2-bromodomain via atomistic simulations disclosing a role of induced fit and conformational selection. Physical Chemistry, Chemical Physics - PCCP, 20(36), 23222-23232
Open this publication in new window or tab >>Mechanistic insights into peptide and ligand binding of the ATAD2-bromodomain via atomistic simulations disclosing a role of induced fit and conformational selection
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2018 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 20, no 36, p. 23222-23232Article in journal (Refereed) Published
Abstract [en]

ATAD2 has emerged as a promising bromodomain (BRD)-containing therapeutic drug target in multiple human cancers. However, recent druggability assessment studies predicted ATAD2's BRD as a target 'difficult to drug' because its binding pocket possesses structural features that are unfeasible for ligand binding. Here, by using all-atom molecular dynamics simulations and an advanced metadynamics method, we demonstrate a dynamic view of the binding pocket features which can hardly be obtained from the "static" crystal data. The most important features disclosed from our simulation data, include: (1) a distinct 'open-to-closed' conformational switch of the ZA loop region in the context of peptide or ligand binding, akin to the induced fit mechanism of molecular recognition, (2) a dynamic equilibrium of the BC loop "in" and "out" conformations, highlighting a role in the conformational selection mechanism for ligand binding, and (3) a new binding region identified distal to the histone-binding pocket that might have implications in bromodomain biology and in inhibitor development. Moreover, based on our simulation results, we propose a model for an "auto-regulatory" mechanism of ATAD2's BRD for histone binding. Overall, the results of this study will not only have implications in bromodomain biology but also provide a theoretical basis for the discovery of new ATAD2's BRD inhibitors.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2018
Keywords
AAA protein, ATAD2 protein, human, DNA binding protein, ligand, peptide, binding site, chemistry, conformation, human, molecular dynamics, ATPases Associated with Diverse Cellular Activities, Binding Sites, DNA-Binding Proteins, Humans, Ligands, Molecular Conformation, Molecular Dynamics Simulation, Peptides
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:kth:diva-236425 (URN)10.1039/c8cp03860k (DOI)000447370600005 ()2-s2.0-85053795262 (Scopus ID)
Note

QC 20181026

Available from: 2018-10-26 Created: 2018-10-26 Last updated: 2018-11-06Bibliographically approved
Kuang, G., Zhou, Y., Zou, R., Halldin, C., Nordberg, A., Långström, B., . . . Tu, Y. (2017). Characterization of the binding mode of the PET tracer [18F]ASEM to a chimera structure of the α7 nicotinic acetylcholine receptor. RSC Advances, 7(32), 19787-19793
Open this publication in new window or tab >>Characterization of the binding mode of the PET tracer [18F]ASEM to a chimera structure of the α7 nicotinic acetylcholine receptor
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2017 (English)In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 7, no 32, p. 19787-19793Article in journal (Refereed) Published
Abstract [en]

The α7 nicotinic acetylcholine receptor (α7-nAChR) is assumed to be implicated in a variety of neurological disorders, such as schizophrenia and Alzheimer's disease (AD). The progress of these disorders can be studied through imaging α7-nAChR with positron emission tomography (PET). [18F]ASEM is a novel and potent α7-nAChR PET radioligand showing great promise in recent tests. However, the mechanism of the molecular interaction between [18F]ASEM and α7-nAChR is still unclear. In this paper, the binding profile of [18F]ASEM to a chimera structure of α7-nAChR was investigated with molecular docking, molecular dynamics, and metadynamics simulation methods. We found that [18F]ASEM binds at the same site as the crystallized agonist epibatidine but with a different binding mode. The dibenzo[b,d]thiophene ring has a different orientation compared to the pyridine ring of epibatidine and has van der Waals interactions with residues from loop C on one side and π-π stacking interaction with Trp53 on the other side. The conformation of Trp53 was found to have a great impact on the binding of [18F]ASEM. Six binding modes in terms of the side chain dihedral angles χ1 and χ2 of Trp53 were discovered by metadynamics simulation. In the most stable binding mode, Trp53 adopts a different conformation from that in the crystalline structure and has a rather favorable π-π stacking interaction with [18F]ASEM. We believe that these discoveries can be valuable for the development of novel PET radioligands.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2017
Keywords
Binding energy, Dihedral angle, Molecular dynamics, Neurodegenerative diseases, Positron emission tomography, Van der Waals forces, Alzheimer's disease, Crystalline structure, Metadynamics simulations, Molecular docking, Neurological disorders, Nicotinic acetylcholine receptors, Positron emission tomography (PET), Van Der Waals interactions, Bins
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-207402 (URN)10.1039/c7ra00496f (DOI)000399242100041 ()2-s2.0-85017176981 (Scopus ID)
Funder
Swedish Foundation for Strategic Research , RB13-0192Stockholm County Council, K1764-2013Swedish National Infrastructure for Computing (SNIC), m.2015-1-396
Note

Funding details: CSC, China Scholarship Council; Funding text: The authors acknowledge support from the Swedish Foundation for Strategic Research (SSF) through the project “New imaging biomarkers in early diagnosis and treatment of Alzheimer's disease (RB13-0192)” and the support from the Stockholm Country Council through the project “Biomolecular profiling for early diagnosis of Alzheimer's disease (K1764-2013)”. Computer time for this work was awarded by a grant from the Swedish Infrastructure Committee (SNIC) for the project “Modeling of protein-ligand binding” (m.2015-1-396). The figures containing molecular structures were rendered with PyMol 1.3 (ref. 51) and VMD 1.9.2 (ref. 52). The work was partly sponsored by the China Scholarship Council (CSC).

QC 20170601

Available from: 2017-06-01 Created: 2017-06-01 Last updated: 2019-05-10Bibliographically approved
Li, S., Zou, R., Tu, Y., Wu, J. & Landry, M. P. (2017). Cholesterol-directed nanoparticle assemblies based on single amino acid peptide mutations activate cellular uptake and decrease tumor volume. Chemical Science, 8(11), 7552-7559
Open this publication in new window or tab >>Cholesterol-directed nanoparticle assemblies based on single amino acid peptide mutations activate cellular uptake and decrease tumor volume
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2017 (English)In: Chemical Science, ISSN 2041-6520, E-ISSN 2041-6539, Vol. 8, no 11, p. 7552-7559Article in journal (Refereed) Published
Abstract [en]

Peptide drugs have been difficult to translate into effective therapies due to their low in vivo stability. Here, we report a strategy to develop peptide-based therapeutic nanoparticles by screening a peptide library differing by single-site amino acid mutations of lysine-modified cholesterol. Certain cholesterol-modified peptides are found to promote and stabilize peptide α-helix formation, resulting in selectively cell-permeable peptides. One cholesterol-modified peptide self-assembles into stable nanoparticles with considerable α-helix propensity stabilized by intermolecular van der Waals interactions between inter-peptide cholesterol molecules, and shows 68.3% stability after incubation with serum for 16 h. The nanoparticles in turn interact with cell membrane cholesterols that are disproportionately present in cancer cell membranes, inducing lipid raft-mediated endocytosis and cancer cell death. Our results introduce a strategy to identify peptide nanoparticles that can effectively reduce tumor volumes when administered to in in vivo mice models. Our results also provide a simple platform for developing peptide-based anticancer drugs.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2017
Keywords
Amino acids, Cell death, Cells, Cholesterol, Cytology, Diagnosis, Diseases, Drug products, Molecular biology, Nanoparticles, Tumors, Van der Waals forces, Amino acid peptides, Anticancer drug, Cell-permeable peptides, Cholesterol molecules, Effective therapy, Membrane cholesterol, Nanoparticle assemblies, Van Der Waals interactions, Peptides
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-222930 (URN)10.1039/c7sc02616a (DOI)000413532800031 ()2-s2.0-85031998089 (Scopus ID)
Note

QC 20180327

Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Wang, Z., Fu, Y., Kang, Z., Liu, X., Chen, N., Wang, Q., . . . Fan, C. (2017). Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton. Journal of the American Chemical Society, 139(44), 15784-15791
Open this publication in new window or tab >>Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton
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2017 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 139, no 44, p. 15784-15791Article in journal (Refereed) Published
Abstract [en]

DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.

Place, publisher, year, edition, pages
American Chemical Society, 2017
Keywords
Biocompatibility, Calcium compounds, Crystalline materials, Medical applications, Nanoparticles, Nucleic acids, Oligonucleotides, Organometallics, Acidic environment, Biomedical applications, Intracellular delivery, Metal organic framework, Metalorganic frameworks (MOFs), Spatiotemporal control, Surface functionalities, Toll-like receptors, DNA, calcium phosphate, cytosine, guanosine, immunostimulating agent, interleukin 6, nanoparticle, oligonucleotide, phosphate, toll like receptor 9, tumor necrosis factor, zirconium, acidity, Article, carbon nuclear magnetic resonance, chemical binding, conformation, controlled study, cytokine release, cytotoxicity, exoskeleton, fluorescence spectroscopy, immunostimulation, immunotherapy, interactions with DNA, RAW 264.7 cell line, transmission electron microscopy, upregulation
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:kth:diva-227052 (URN)10.1021/jacs.7b07895 (DOI)2-s2.0-85033219489 (Scopus ID)
Note

QC 20180503

Available from: 2018-05-03 Created: 2018-05-03 Last updated: 2018-05-03Bibliographically approved
Kuang, G., Bulone, V. & Tu, Y. (2016). Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P-3 with the pleckstrin homology domain of an oomycete cellulose synthase. Scientific Reports, 6, Article ID 20555.
Open this publication in new window or tab >>Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P-3 with the pleckstrin homology domain of an oomycete cellulose synthase
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 20555Article in journal (Refereed) Published
Abstract [en]

Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. S. monoica contains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. Understanding the molecular interactions between the PH domain and phosphoinositides would help to unravel the cellulose biosynthesis process of oomycetes. In this work, the binding profile of PtdIns (3,4,5) P-3, a typical phosphoinositide, with SmCesA2-PH was studied by molecular docking, molecular dynamics and metadynamics simulations. PtdIns (3,4,5) P-3 is found to bind at a specific site located at beta 1, beta 2 and beta 1-beta 2 loop of SmCesA2-PH. The high affinity of PtdIns (3,4,5) P-3 to SmCesA2-PH is contributed by the free phosphate groups, which have electrostatic and hydrogenbond interactions with Lys88, Lys100 and Arg102 in the binding site.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-183190 (URN)10.1038/srep20555 (DOI)000369579200001 ()26857031 (PubMedID)2-s2.0-84957551924 (Scopus ID)
Note

QC 20160303

Available from: 2016-03-03 Created: 2016-03-03 Last updated: 2017-11-30Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8198-9284

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