Displaying all 5 publications

  1. Tan CY, Rahman RN, Kadir HA, Tayyab S
    Acta Biochim. Pol., 2011;58(3):405-12.
    PMID: 21887412
    Bacillus licheniformis α-amylase (BLA) was chemically modified using 100-fold molar excess of succinic anhydride over protein or 0.66 M potassium cyanate to obtain 42 % succinylated and 81 % carbamylated BLAs. Size and charge homogeneity of modified preparations was established by Sephacryl S-200 HR gel chromatography and polyacrylamide gel electrophoresis. Conformational alteration in these preparations was evident by the larger Stokes radii (3.40 nm for carbamylated and 3.34 nm for succinylated BLAs) compared to 2.43 nm obtained for native BLA. Urea denaturation results using mean residue ellipticity (MRE) as a probe also showed conformational destabilization based on the early start of transition as well as ΔG(D)(H(2)O) values obtained for both modified derivatives and Ca-depleted BLA. Decrease in ΔG(D)(H(2)O) value from 5,930 cal/mol (for native BLA) to 3,957 cal/mol (for succinylated BLA), 3,336 cal/mol (for carbamylated BLA) and 3,430 cal/mol for Ca-depleted BLA suggested reduced conformational stability upon modification of amino groups of BLA or depletion of calcium. Since both succinylation and carbamylation reactions abolish the positive charge on amino groups (both α- and ε- amino), the decrease in conformational stability can be ascribed to the disruption of salt bridges present in the protein which might have released the intrinsic calcium from its binding site.
    Matched MeSH terms: Lysine/chemistry
  2. Tejo BA, Salleh AB, Pleiss J
    J Mol Model, 2004 Dec;10(5-6):358-66.
    PMID: 15597204
    The effect of organic solvent on the structure and dynamics of proteins was investigated by multiple molecular dynamics simulations (1 ns each) of Candida rugosa lipase in water and in carbon tetrachloride. The choice of solvent had only a minor structural effect. For both solvents the open and the closed conformation of the lipase were near to their experimental X-ray structures (C(alpha) rms deviation 1-1.3 A). However, the solvents had a highly specific effect on the flexibility of solvent-exposed side chains: polar side chains were more flexible in water, but less flexible in organic solvent. In contrast, hydrophobic residues were more flexible in organic solvent, but less flexible in water. As a major effect solvent changed the dynamics of the lid, a mobile element involved in activation of the lipase, which fluctuated as a rigid body about its average position. While in water the deviations were about 1.6 A, organic solvent reduced flexibility to 0.9 A. This increase rigidity was caused by two salt bridges (Lys85-Asp284, Lys75-Asp79) and a stable hydrogen bond (Lys75-Asn 292) in organic solvent. Thus, organic solvents stabilize the lid but render the side chains in the hydrophobic substrate-binding site more mobile. [figure: see text]. Superimposition of open (black, PDB entry 1CRL) and closed (gray, PDB entry 1TRH) conformers of C. rugosa lipase. The mobile lid is indicated.
    Matched MeSH terms: Lysine/chemistry
  3. Ahmad NN, Ahmad Kamarudin NH, Leow ATC, Rahman RNZRA
    Molecules, 2020 Aug 25;25(17).
    PMID: 32854267 DOI: 10.3390/molecules25173858
    Surface charge residues have been recognized as one of the stability determinants in protein. In this study, we sought to compare and analyse the stability and conformational dynamics of staphylococcal lipase mutants with surface lysine mutation using computational and experimental methods. Three highly mutable and exposed lysine residues (Lys91, Lys177, Lys325) were targeted to generate six mutant lipases in silico. The model structures were simulated in water environment at 25 °C. Our simulations showed that the stability was compromised when Lys177 was substituted while mutation at position 91 and 325 improved the stability. To illustrate the putative alterations of enzyme stability in the stabilising mutants, we characterized single mutant K325G and double mutant K91A/K325G. Both mutants showed a 5 °C change in optimal temperature compared to their wild type. Single mutant K325G rendered a longer half-life at 25 °C (T1/2 = 21 h) while double mutant K91A/K325G retained only 40% of relative activity after 12 h incubation. The optimal pH for mutant K325G was shifted from 8 to 9 and similar substrate preference was observed for the wild type and two mutants. Our findings indicate that surface lysine mutation alters the enzymatic behaviour and, thus, rationalizes the functional effects of surface exposed lysine in conformational stability and activity of this lipase.
    Matched MeSH terms: Lysine/chemistry
  4. Kueh R, Rahman NA, Merican AF
    J Mol Model, 2003 Apr;9(2):88-98.
    PMID: 12707802
    The arginine repressor (ArgR) of Escherichia coli binds to six L-arginine molecules that act as its co-repressor in order to bind to DNA. The binding of L-arginine molecules as well as its structural analogues is compared by means of computational docking. A grid-based energy evaluation method combined with a Monte Carlo simulated annealing process was used in the automated docking. For all ligands, the docking procedure proposed more than one binding site in the C-terminal domain of ArgR (ArgRc). Interaction patterns of ArgRc with L-arginine were also observed for L-canavanine and L-citrulline. L-lysine and L-homoarginine, on the other hand, were shown to bind poorly at the binding site. Figure A general overview of the sites found from docking the various ligands into ArgRc ( grey ribbons). Red coloured sticks: residues in binding site H that was selected for docking
    Matched MeSH terms: Lysine/chemistry
  5. Zare-Zardini H, Taheri-Kafrani A, Amiri A, Bordbar AK
    Sci Rep, 2018 01 12;8(1):586.
    PMID: 29330486 DOI: 10.1038/s41598-017-18938-y
    In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2) and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell lines. The percentage of apoptotic cells was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The hemolysis and blood coagulation activity of nanostructures were performed. Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active against cancer cell lines in comparison with their cytotoxic activity against normal cell lines (MSCs) with IC50 values higher than 100 μg/ml. The results of TUNEL assay indicates a significant increase in the rates of TUNEL positive cells by increasing the concentrations of nanomaterials. Results were also shown that aggregation and changes of RBCs morphology were occurred in the presence of GO, GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had effect on blood coagulation system, especially on PTT. All nanostrucure act as antitumor drug so that binding of drugs to a nostructures is irresolvable and the whole structure enter to the cell as a drug.
    Matched MeSH terms: Lysine/chemistry
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