Displaying publications 101 - 120 of 305 in total

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  1. Fulltext Curculin exhibits sweet-tasting and taste-modifying activities through its distinct molecular surfaces
    Kurimoto E, Suzuki M, Amemiya E, Yamaguchi Y, Nirasawa S, Shimba N, et al.
    J Biol Chem, 2007 Nov 16;282(46):33252-33256.
    PMID: 17895249 DOI: 10.1074/jbc.C700174200
    Curculin isolated from Curculigo latifolia, a plant grown in Malaysia, has an intriguing property of modifying sour taste into sweet taste. In addition to this taste-modifying activity, curculin itself elicits a sweet taste. Although these activities have been attributed to the heterodimeric isoform and not homodimers of curculin, the underlying mechanisms for the dual action of this protein have been largely unknown. To identify critical sites for these activities, we performed a mutational and structural study of recombinant curculin. Based on the comparison of crystal structures of curculin homo- and heterodimers, a series of mutants was designed and subjected to tasting assays. Mapping of amino acid residues on the three-dimensional structure according to their mutational effects revealed that the curculin heterodimer exhibits sweet-tasting and taste-modifying activities through its partially overlapping but distinct molecular surfaces. These findings suggest that the two activities of the curculin heterodimer are expressed through its two different modes of interactions with the T1R2-T1R3 heterodimeric sweet taste receptor.
    Matched MeSH terms: Protein Binding
  2. Fulltext Identification of Potential Inhibitors of 3CL Protease of SARS-CoV-2 From ZINC Database by Molecular Docking-Based Virtual Screening
    Abdusalam AAA, Murugaiyah V
    Front Mol Biosci, 2020;7:603037.
    PMID: 33392261 DOI: 10.3389/fmolb.2020.603037
    The rapid outbreak of Coronavirus Disease 2019 (COVID-19) that was first identified in Wuhan, China is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The 3CL protease (3CLpro) is the main protease of the SARS-CoV-2, which is responsible for the viral replication and therefore considered as an attractive drug target since to date there is no specific and effective vaccine available against this virus. In this paper, we reported molecular docking-based virtual screening (VS) of 2000 compounds obtained from the ZINC database and 10 FDA-approved (antiviral and anti-malaria) on 3CLpro using AutoDock Vina to find potential inhibitors. The screening results showed that the top four compounds, namely ZINC32960814, ZINC12006217, ZINC03231196, and ZINC33173588 exhibited high affinity at the 3CLpro binding pocket. Their free energy of binding (FEB) were -12.3, -11.9, -11.7, and -11.2 kcal/mol while AutoDock Vina scores were -12.61, -12.32, -12.01, and -11.92 kcal/mol, respectively. These results were better than the co-crystallized ligand N3, whereby its FEB was -7.5 kcal/mol and FDA-approved drugs. Different but stable interactions were obtained between the four identified compounds with the catalytic dyad residues of the 3CLpro. In conclusion, novel 3CLpro inhibitors from the ZINC database were successfully identified using VS and molecular docking approach, fulfilling the Lipinski rule of five, and having low FEB and functional molecular interactions with the target protein. The findings suggests that the identified compounds may serve as potential leads that act as COVID-19 3CLpro inhibitors, worthy for further evaluation and development.
    Matched MeSH terms: Protein Binding
  3. Protein-Protein Interactions of Phosphodiesterases
    Al-Nema MY, Gaurav A
    Curr Top Med Chem, 2019;19(7):555-564.
    PMID: 30931862 DOI: 10.2174/1568026619666190401113803
    BACKGROUND: Phosphodiesterases (PDEs) are enzymes that play a key role in terminating cyclic nucleotides signalling by catalysing the hydrolysis of 3', 5'- cyclic adenosine monophosphate (cAMP) and/or 3', 5' cyclic guanosine monophosphate (cGMP), the second messengers within the cell that transport the signals produced by extracellular signalling molecules which are unable to get into the cells. However, PDEs are proteins which do not operate alone but in complexes that made up of a many proteins.

    OBJECTIVE: This review highlights some of the general characteristics of PDEs and focuses mainly on the Protein-Protein Interactions (PPIs) of selected PDE enzymes. The objective is to review the role of PPIs in the specific mechanism for activation and thereby regulation of certain biological functions of PDEs.

    METHODS: The article discusses some of the PPIs of selected PDEs as reported in recent scientific literature. These interactions are critical for understanding the biological role of the target PDE.

    RESULTS: The PPIs have shown that each PDE has a specific mechanism for activation and thereby regulation a certain biological function.

    CONCLUSION: Targeting of PDEs to specific regions of the cell is based on the interaction with other proteins where each PDE enzyme binds with specific protein(s) via PPIs.

    Matched MeSH terms: Protein Binding
  4. Molecular analysis of Hsp70 mechanisms in plants and their function in response to stress
    Usman MG, Rafii MY, Martini MY, Yusuff OA, Ismail MR, Miah G
    Biotechnol Genet Eng Rev, 2017 Apr;33(1):26-39.
    PMID: 28649918 DOI: 10.1080/02648725.2017.1340546
    Studying the strategies of improving abiotic stress tolerance is quite imperative and research under this field will increase our understanding of response mechanisms to abiotic stress such as heat. The Hsp70 is an essential regulator of protein having the tendency to maintain internal cell stability like proper folding protein and breakdown of unfolded proteins. Hsp70 holds together protein substrates to help in movement, regulation, and prevent aggregation under physical and or chemical pressure. However, this review reports the molecular mechanism of heat shock protein 70 kDa (Hsp70) action and its structural and functional analysis, research progress on the interaction of Hsp70 with other proteins and their interaction mechanisms as well as the involvement of Hsp70 in abiotic stress responses as an adaptive defense mechanism.
    Matched MeSH terms: Protein Binding
  5. Theoretical analyses on enantiospecificity of L-2-haloacid dehalogenase (DehL) from Rhizobium sp. RC1 towards 2-chloropropionic acid
    Adamu A, Abdul Wahab R, Aliyu F, Abdul Razak FI, Mienda BS, Shamsir MS, et al.
    J Mol Graph Model, 2019 11;92:131-139.
    PMID: 31352207 DOI: 10.1016/j.jmgm.2019.07.012
    Dehalogenases continue to garner interest of the scientific community due to their potential applications in bioremediation of halogen-contaminated environment and in synthesis of various industrially relevant products. Example of such enzymes is DehL, an L-2-haloacid dehalogenase (EC 3.8.1.2) from Rhizobium sp. RC1 that catalyses the specific cleavage of halide ion from L-2-halocarboxylic acids to produce the corresponding D-2-hydroxycarboxylic acids. Recently, the catalytic residues of DehL have been identified and its catalytic mechanism has been fully elucidated. However, the enantiospecificity determinants of the enzyme remain unclear. This information alongside a well-defined catalytic mechanism are required for rational engineering of DehL for substrate enantiospecificity. Therefore, using quantum mechanics/molecular mechanics and molecular mechanics Poisson-Boltzmann surface area calculations, the current study theoretically investigated the molecular basis of DehL enantiospecificity. The study found that R51L mutation cancelled out the dehalogenation activity of DehL towards it natural substrate, L-2-chloropropionate. The M48R mutation, however introduced a new activity towards D-2-chloropropionate, conveying the possibility of inverting the enantiospecificity of DehL from L-to d-enantiomer with a minimum of two simultaneous mutations. The findings presented here will play important role in the rational design of DehL dehalogenase for improving substrate utility.
    Matched MeSH terms: Protein Binding
  6. Toward activated homology models of the human M1 muscarinic acetylcholine receptor
    Chin SP, Buckle MJ, Chalmers DK, Yuriev E, Doughty SW
    J Mol Graph Model, 2014 Apr;49:91-8.
    PMID: 24631873 DOI: 10.1016/j.jmgm.2014.02.002
    Structure-based virtual screening offers a good opportunity for the discovery of selective M1 muscarinic acetylcholine receptor (mAChR) agonists for the treatment of Alzheimer's disease. However, no 3-D structure of an M1 mAChR is yet available and the homology models that have been previously reported are only able to identify antagonists in virtual screening experiments. In this study, we generated a homology model of the human M1 mAChR, based on the crystal structure of an M3 mAChR as the template. This initial model was modified, using the agonist-bound crystal structure of a β2-adrenergic receptor as a guide, to give two possible activated structures. The T192 side chain was adjusted in both structures and one of the structures also had the whole of transmembrane (TM) 5 rotated and tilted toward the inner channel of the transmembrane region. The binding sites of all three structures were then refined by induced-fit docking (IFD) with acetylcholine. Virtual screening experiments showed that all three refined models could efficiently differentiate agonists from decoy molecules, with the TM5-modified models also giving good agonist/antagonist selectivity. The whole range of agonists and antagonists was observed to bind within the orthosteric site of the structure obtained by IFD refinement alone, implying that it has inactive state character. In contrast, the two TM5-modified structures were unable to accommodate the antagonists, supporting the proposition that they possess activated state character.
    Matched MeSH terms: Protein Binding
  7. Conformational and energy evaluations of novel peptides binding to dengue virus envelope protein
    Amir-Hassan A, Lee VS, Baharuddin A, Othman S, Xu Y, Huang M, et al.
    J Mol Graph Model, 2017 06;74:273-287.
    PMID: 28458006 DOI: 10.1016/j.jmgm.2017.03.010
    Effective novel peptide inhibitors which targeted the domain III of the dengue envelope (E) protein by blocking dengue virus (DENV) entry into target cells, were identified. The binding affinities of these peptides towards E-protein were evaluated by using a combination of docking and explicit solvent molecular dynamics (MD) simulation methods. The interactions of these complexes were further investigated by using the Molecular Mechanics-Poisson Boltzmann Surface Area (MMPBSA) and Molecular Mechanics Generalized Born Surface Area (MMGBSA) methods. Free energy calculations of the peptides interacting with the E-protein demonstrated that van der Waals (vdW) and electrostatic interactions were the main driving forces stabilizing the complexes. Interestingly, calculated binding free energies showed good agreement with the experimental dissociation constant (Kd) values. Our results also demonstrated that specific residues might play a crucial role in the effective binding interactions. Thus, this study has demonstrated that a combination of docking and molecular dynamics simulations can accelerate the identification process of peptides as potential inhibitors of dengue virus entry into host cells.
    Matched MeSH terms: Protein Binding
  8. Binding Hotspot and Activation Mechanism of Maltitol and Lactitol toward the Human Sweet Taste Receptor
    Mahalapbutr P, Lee VS, Rungrotmongkol T
    J Agric Food Chem, 2020 Jul 29;68(30):7974-7983.
    PMID: 32551626 DOI: 10.1021/acs.jafc.0c02580
    Human sweet taste receptor (hSTR) recognizes a wide array of sweeteners, resulting in sweet taste perception. Maltitol and lactitol have been extensively used in place of sucrose due to their capability to prevent dental caries. Herein, several molecular modeling approaches were applied to investigate the structural and energetic properties of these two polyols/hSTR complexes. Triplicate 500 ns molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM/GBSA)-based free energy calculations revealed that the TAS1R2 monomer is the preferential binding site for maltitol and lactitol rather than the TAS1R3 region. Several polar residues (D142, S144, Y215, D278, E302, R383, and especially N143) were involved in polyols binding through electrostatic attractions and H-bond formations. The molecular complexation process not only induced the stable form of ligands but also stimulated the conformational adaptation of the TAS1R2 monomer to become a close-packed structure through an induced-fit mechanism. Notably, the binding affinity of the maltitol/TAS1R2 complex (ΔGbind of -17.93 ± 1.49 kcal/mol) was significantly higher than that of the lactitol/TAS1R2 system (-8.53 ± 1.78 kcal/mol), in line with the experimental relative sweetness. These findings provide an in-depth understanding of the differences in the sweetness response between maltitol and lactitol, which could be helpful to design novel polyol derivatives with higher sweet taste perception.
    Matched MeSH terms: Protein Binding
  9. Fulltext The Sequence-specific Peptide-binding Activity of the Protein Sulfide Isomerase AGR2 Directs Its Stable Binding to the Oncogenic Receptor EpCAM
    Mohtar MA, Hernychova L, O'Neill JR, Lawrence ML, Murray E, Vojtesek B, et al.
    Mol Cell Proteomics, 2018 04;17(4):737-763.
    PMID: 29339412 DOI: 10.1074/mcp.RA118.000573
    AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a specific peptide motif (TTIYY). A synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for AGR2 by measuring its activity against a mutant peptide library. Screening the human proteome for proteins harboring this motif revealed an enrichment in transmembrane proteins and we focused on validating EpCAM as a potential AGR2-interacting protein. AGR2 and EpCAM proteins formed a dose-dependent protein-protein interaction in vitro Proximity ligation assays demonstrated that endogenous AGR2 and EpCAM protein associate in cells. Introducing a single alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a stable binding site for AGR2 on EpCAM, adjacent to the TLIYY motif and surrounding EpCAM's detergent binding site. These data define a dominant site on AGR2 that mediates its specific peptide-binding function. EpCAM forms a model client protein for AGR2 to study how an ER-resident chaperone can dock specifically to a peptide motif and regulate the trafficking a protein destined for the secretory pathway.
    Matched MeSH terms: Protein Binding
  10. Fulltext A comparative analysis on the binding characteristics of various mammalian albumins towards a multitherapeutic agent, pinostrobin
    Feroz SR, Sumi RA, Malek SN, Tayyab S
    Exp Anim, 2015;64(2):101-8.
    PMID: 25519455 DOI: 10.1538/expanim.14-0053
    The interaction of pinostrobin (PS), a multitherapeutic agent with serum albumins of various mammalian species namely, goat, bovine, human, porcine, rabbit, sheep and dog was investigated using fluorescence quench titration and competitive drug displacement experiments. Analysis of the intrinsic fluorescence quenching data revealed values of the association constant, K(a) in the range of 1.49 - 6.12 × 10(4) M(-1), with 1:1 binding stoichiometry. Based on the PS-albumin binding characteristics, these albumins were grouped into two classes. Ligand displacement studies using warfarin as the site I marker ligand correlated well with the binding data. Albumins from goat and bovine were found to be closely similar to human albumin on the basis of PS binding characteristics.
    Matched MeSH terms: Protein Binding
  11. Anti-Cholinesterase Activity of Chalcone Derivatives: Synthesis, In Vitro Assay and Molecular Docking Study
    Riswanto FDO, Rawa MSA, Murugaiyah V, Salin NH, Istyastono EP, Hariono M, et al.
    Med Chem, 2021;17(5):442-452.
    PMID: 31808389 DOI: 10.2174/1573406415666191206095032
    BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase).

    OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

    METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method.

    RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288.

    CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.

    Matched MeSH terms: Protein Binding
  12. Fulltext The multifarious roles of heterogeneous ribonucleoprotein A1 in viral infections
    Kaur R, Lal SK
    Rev Med Virol, 2020 03;30(2):e2097.
    PMID: 31989716 DOI: 10.1002/rmv.2097
    Viruses are obligate parasites known to interact with a wide variety of host proteins at different stages of infection. Current antiviral treatments target viral proteins and may be compromised due to the emergence of drug resistant viral strains. Targeting viral-host interactions is now gaining recognition as an alternative approach against viral infections. Recent research has revealed that heterogeneous ribonucleoprotein A1, an RNA-binding protein, plays an essential functional and regulatory role in the life cycle of many viruses. In this review, we summarize the interactions between heterogeneous ribonucleoprotein A1 (hnRNPA1) and multiple viral proteins during the life cycle of RNA and DNA viruses. hnRNPA1 protein levels are modulated differently, in different viruses, which further dictates its stability, function, and intracellular localization. Multiple reports have emphasized that in Sindbis virus, enteroviruses, porcine endemic diarrhea virus, and rhinovirus infection, hnRNPA1 enhances viral replication and survival. However, in others like hepatitis C virus and human T-cell lymphotropic virus, it exerts a protective response. The involvement of hnRNPA1 in viral infections highlights its importance as a central regulator of host and viral gene expression. Understanding the nature of these interactions will increase our understanding of specific viral infections and pathogenesis and eventually aid in the development of novel and robust antiviral intervention strategies.
    Matched MeSH terms: Protein Binding
  13. The effect of multiple simulation parameters on MM/PBSA performance for binding affinity prediction of CB1 cannabinoid receptor agonists and antagonists
    Loo JSE, Yong AYY, Yong YN
    Chem Biol Drug Des, 2020 11;96(5):1244-1254.
    PMID: 32462752 DOI: 10.1111/cbdd.13733
    Both the inactive- and active-state CB1 receptor crystal structures have now been solved, allowing their application in various structure-based drug design methods. One potential method utilizing these crystal structures is the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method of predicting relative binding free.
    Matched MeSH terms: Protein Binding
  14. Fulltext Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines
    Sim EU, Chan SL, Ng KL, Lee CW, Narayanan K
    Dis Markers, 2016;2016:5179594.
    PMID: 28018022 DOI: 10.1155/2016/5179594
    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.
    Matched MeSH terms: Protein Binding
  15. In Silico Docking of Vitamin E Isomers on Transport Proteins
    Zulkiflee NS, Awang SA, Ming WX, Kamilan MFW, Mariappan MY, Kit TJ
    Curr Comput Aided Drug Des, 2020;16(4):467-472.
    PMID: 31203808 DOI: 10.2174/1573409915666190614113733
    BACKGROUND: Vitamin E is comprised of α, β, γ and δ-tocopherols (Ts) and α, β, γ and δ- tocotrienols (T3s). Vitamin E has neuroprotective antioxidant, anti-cancer, and cholesterol-lowering effects. Intracellular trafficking of these isomers remains largely unknown, except for αT which is selectively transported by αT transfer protein (αTTP).

    OBJECTIVE: This study aimed to determine the binding of vitamin E isomers on transport proteins using in silico docking.

    METHODS: Transport proteins were selected using AmiGo Gene Ontology tool based on the same molecular function annotation as αTTP. Protein structures were obtained from the Protein Data Bank. Ligands structures were obtained from ZINC database. In silico docking was performed using SwissDock.

    RESULTS AND DISCUSSION: A total of 6 transport proteins were found: SEC14-like protein 2, glycolipid transfer protein (GLTP), pleckstrin homology domain-containing family A member 8, collagen type IV alpha-3-binding protein, ceramide-1-phosphate transfer protein and afamin. Compared with other transport proteins, αTTP had the highest affinities for all isomers except βT3. Binding order of vitamin E isomers toward αTTP was γT > βT > αT > δT > αT3 > γT3 > δT3 > βT3. GLTP had a higher affinity for tocotrienols than tocopherols. βT3 bound stronger to GLTP than αTTP.

    CONCLUSION: αTTP remained as the most preferred transport protein for most of the isomers. The binding affinity of αT toward αTTP was not the highest than other isomers suggested that other intracellular trafficking mechanisms of these isomers may exist. GLTP may mediate the intracellular transport of tocotrienols, especially βT3. Improving the bioavailability of these isomers may enhance their beneficial effects to human.

    Matched MeSH terms: Protein Binding
  16. Development, characterization and pharmacokinetics of mupirocin-loaded nanostructured lipid carriers (NLCs) for intravascular administration
    Alcantara KP, Zulfakar MH, Castillo AL
    Int J Pharm, 2019 Nov 25;571:118705.
    PMID: 31536765 DOI: 10.1016/j.ijpharm.2019.118705
    Mupirocin is a promising broad-spectrum antibiotic that is effective in treating MRSA infections. However, due to its rapid elimination and hydrolysis following injection and high protein binding, current therapeutic use is limited to topical administration. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug degradation by encapsulation. The objective of this research is to develop and characterize Mupirocin-Loaded Nanostructured Lipid Carriers (M-NLC) for intravascular administration. The MNLC was produced by a combination of high shear homogenization and high pressure homogenization of solid (cetyl palmitate) and liquid (caprylic/caprylic acid) biocompatible lipids in 5 different ratios. The mean particle size, polydispersity index (PDI) and the zeta potential (ZP) of the MNLC formulations were between 99.8 and 235 nm, PDI lower than 0.164, ZP from -25.96 to -19.53 and pH ranging from 6.28-6.49. The MNLC formulation also enhances the anti-bacterial activity of mupirocin. All formulation showed sustained drug release and good physical characteristics for three months storage under 25 °C. It also revealed that the MNLC 1 is safe at 250 mg/kg dose in rats. The MNLC 1 also showed a significant increase in plasma concentration in rabbits following IV administration thus, demonstrating an enhancement on its pharmacokinetic profile as compared to free mupirocin.
    Matched MeSH terms: Protein Binding
  17. Binding of an anticancer drug, axitinib to human serum albumin: Fluorescence quenching and molecular docking study
    Tayyab S, Izzudin MM, Kabir MZ, Feroz SR, Tee WV, Mohamad SB, et al.
    J. Photochem. Photobiol. B, Biol., 2016 Sep;162:386-94.
    PMID: 27424099 DOI: 10.1016/j.jphotobiol.2016.06.049
    Binding characteristics of a promising anticancer drug, axitinib (AXT) to human serum albumin (HSA), the major transport protein in human blood circulation, were studied using fluorescence, UV-vis absorption and circular dichroism (CD) spectroscopy as well as molecular docking analysis. A gradual decrease in the Stern-Volmer quenching constant with increasing temperature revealed the static mode of the protein fluorescence quenching upon AXT addition, thus confirmed AXT-HSA complex formation. This was also confirmed from alteration in the UV-vis spectrum of HSA upon AXT addition. Fluorescence quenching titration results demonstrated moderately strong binding affinity between AXT and HSA based on the binding constant value (1.08±0.06×10(5)M(-1)), obtained in 10mM sodium phosphate buffer, pH7.4 at 25°C. The sign and magnitude of the enthalpy change (∆H=-8.38kJmol(-1)) as well as the entropy change (∆S=+68.21Jmol(-1)K(-1)) clearly suggested involvement of both hydrophobic interactions and hydrogen bonding in AXT-HSA complex formation. These results were well supported by molecular docking results. Three-dimensional fluorescence spectral results indicated significant microenvironmental changes around Trp and Tyr residues of HSA upon complexation with AXT. AXT binding to the protein produced significant alterations in both secondary and tertiary structures of HSA, as revealed from the far-UV and the near-UV CD spectral results. Competitive drug displacement results obtained with phenylbutazone (site I marker), ketoprofen (site II marker) and hemin (site III marker) along with molecular docking results suggested Sudlow's site I, located in subdomain IIA of HSA, as the preferred binding site of AXT.
    Matched MeSH terms: Protein Binding
  18. Multi-template homology-based structural model of L-2-haloacid dehalogenase (DehL) from Rhizobium sp. RC1
    Adamu A, Shamsir MS, Wahab RA, Parvizpour S, Huyop F
    J Biomol Struct Dyn, 2017 Nov;35(15):3285-3296.
    PMID: 27800712 DOI: 10.1080/07391102.2016.1254115
    Dehalogenases are of high interest due to their potential applications in bioremediation and in synthesis of various industrial products. DehL is an L-2-haloacid dehalogenase (EC 3.8.1.2) that catalyses the cleavage of halide ion from L-2-halocarboxylic acid to produce D-2-hydroxycarboxylic acid. Although DehL utilises the same substrates as the other L-2-haloacid dehalogenases, its deduced amino acid sequence is substantially different (<25%) from those of the rest L-2-haloacid dehalogenases. To date, the 3D structure of DehL is not available. This limits the detailed understanding of the enzyme's reaction mechanism. The present work predicted the first homology-based model of DehL and defined its active site. The monomeric unit of the DehL constitutes α/β structure that is organised into two distinct structural domains: main and subdomains. Despite the sequence disparity between the DehL and other L-2-haloacid dehalogenases, its structural model share similar fold as the experimentally solved L-DEX and DehlB structures. The findings of the present work will play a crucial role in elucidating the molecular details of the DehL functional mechanism.
    Matched MeSH terms: Protein Binding
  19. Fulltext Xeno-free culture of human pluripotent stem cells on oligopeptide-grafted hydrogels with various molecular designs
    Chen YM, Chen LH, Li MP, Li HF, Higuchi A, Kumar SS, et al.
    Sci Rep, 2017 03 23;7:45146.
    PMID: 28332572 DOI: 10.1038/srep45146
    Establishing cultures of human embryonic (ES) and induced pluripotent (iPS) stem cells in xeno-free conditions is essential for producing clinical-grade cells. Development of cell culture biomaterials for human ES and iPS cells is critical for this purpose. We designed several structures of oligopeptide-grafted poly (vinyl alcohol-co-itaconic acid) hydrogels with optimal elasticity, and prepared them in formations of single chain, single chain with joint segment, dual chain with joint segment, and branched-type chain. Oligopeptide sequences were selected from integrin- and glycosaminoglycan-binding domains of the extracellular matrix. The hydrogels grafted with vitronectin-derived oligopeptides having a joint segment or a dual chain, which has a storage modulus of 25 kPa, supported the long-term culture of human ES and iPS cells for over 10 passages. The dual chain and/or joint segment with cell adhesion molecules on the hydrogels facilitated the proliferation and pluripotency of human ES and iPS cells.
    Matched MeSH terms: Protein Binding
  20. Comprehensive insight into the binding of sunitinib, a multi-targeted anticancer drug to human serum albumin
    Kabir MZ, Tee WV, Mohamad SB, Alias Z, Tayyab S
    Spectrochim Acta A Mol Biomol Spectrosc, 2017 Jun 15;181:254-263.
    PMID: 28376387 DOI: 10.1016/j.saa.2017.03.059
    Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×104M-1), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
    Matched MeSH terms: Protein Binding
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