Evidence for the role of the α-helix in the xylosylation reactions involving the glycosaminoglycan-bearing serine of decorin/DS-PGII as shown by 1H NMR, CD, and molecular modeling studies

1996 ◽  
Vol 74 (3) ◽  
pp. 389-401 ◽  
Author(s):  
Yunjun Wang ◽  
Jan Sejbal ◽  
George Kotovych ◽  
Paul G. Scott
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Water Mixture ◽  
Terminal Sequence ◽  
Trans Isomers ◽  
Methionine Residue ◽  
Nmr Techniques ◽  
Molecular Modeling Studies ◽  
Α Helix

The conformation of four peptides (N-terminal acetylated and unacetylated 14-mers DEASGIGPEEHFPENH2 and 24-mers AcQKGLFDFMLEDEASGIGPEEHFPENH2 with a normal and an oxidized methionine residue) containing the sequence Asp-Glu-Ala-Ser-Gly-Ile-Gly (DEASGIG), which is known to play an important role in the xylosylation reactions involving the glycosaminoglycan-bearing serine of decorin/DS-PGII, were studied by two-dimensional proton NMR techniques, circular dichroism spectroscopy, and molecular dynamics in a methanol–water mixture. The 14-residue peptide comprises the first (i.e., N-terminal) 14 amino acids of the mature decorin protein and the 24-residue peptide incorporates an additional (N-terminal) sequence of 10 amino acids derived from the procore of decorin. The resonance heterogeneity induced by the isomerization of the two prolines (Pro8, Pro13 in the 14-mer, and Pro18, Pro23 in the 24-mer) in the peptides studied was evaluated from TOCSY and NOESY NMR spectra. The trans-trans, trans-cis, and cis-trans isomers exist in approximate 68:25:7 proportions in the methanol–water mixture. The NOE distance constraints were used as input parameters for molecular dynamics and restrained energy minimization calculations. It was demonstrated that the conformation of the DEASGIG fragment was affected by the presence of the 10 amino acids at the N-terminal end of the 24-mer, and that the serine is part of an α-helix. The results indicate that an α-helix is present in the 24-mer beginning at the N-terminal end with Lys2 and ending at Gly15, and suggest that this could be the signal for the xylosylation of serine Ser14. A type VIb β turn was observed, involving the C-terminal cis-proline in the sequence His-Phe-Pro-Glu. Key words: xylosylation, nascent helix, α-helix, csi-proline, type VIb β-turn, molecular dynamics.

scholarly journals Deformation twinning and the role of amino acids and magnesium in calcite hardness from molecular simulation

2015 ◽  
Vol 17 (31) ◽  
pp. 20178-20184 ◽  
Author(s):  
A. S. Côté ◽  
R. Darkins ◽  
D. M. Duffy
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Molecular Simulation ◽  
Elastic Properties ◽  
Deformation Twinning ◽  
Pure Crystal ◽  
Classical Molecular Dynamics ◽  
Deformation Twins

We employ classical molecular dynamics to calculate elastic properties and to model the nucleation and propagation of deformation twins in calcite, both as a pure crystal and with magnesium and aspartate inclusions.

Potent cyclometallated Pd(ii) antitumor complexes bearing α-amino acids: synthesis, structural characterization, DNA/BSA binding, cytotoxicity and molecular dynamics simulation

2020 ◽  
Vol 49 (42) ◽  
pp. 14891-14907
Author(s):  
Sedigheh Abedanzadeh ◽  
Kazem Karami ◽  
Mostafa Rahimi ◽  
Masoud Edalati ◽  
Mozhgan Abedanzadeh ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Molecular Modeling ◽  
Molecular Dynamics Simulation ◽  
Structural Characterization ◽  
Dynamics Simulation ◽  
Bsa Binding ◽  
Modeling Studies ◽  
Molecular Modeling Studies ◽  
Antitumor Complexes

Synthesis, characterization, spectroscopic, biological, and molecular modeling studies on the DNA/BSA binding interactions of new cyclometallated Pd(ii) complexes bearing α-amino acids were investigated.

Methionine aminopeptidases and angiogenesis

2002 ◽  
Vol 38 ◽  
pp. 65-78 ◽  
Author(s):  
Ralph A Bradshaw ◽  
Elizabeth Yi
Keyword(s):  
Cell Cycle ◽  
Amino Acids ◽  
Cancer Cells ◽  
Protease Activity ◽  
Single Gene ◽  
Covalent Modification ◽  
Methionine Aminopeptidase ◽  
Methionine Residue ◽  
Methionine Aminopeptidases

The initiator methionine residue of proteins is removed during synthesis by a specific and ubiquitous enzyme, methionine aminopeptidase (MetAP). Prokaryotes have a single gene, while eukaryotes have two isoforms. This family of metalloenzymes generally cleaves substrates in which the penultimate residue is one of the seven smaller amino acids (glycine, alanine, serine, threonine, proline, cysteine and valine). One of the eukaryotic isoforms (MetAP2) has an additional non-proteolytic function and is the principle target of a family of anti-angiogenic drugs that are related to fumagillin. The resulting covalent modification inhibits the protease activity of MetAP2 and blocks cell-cycle function in endothelial and some cancer cells. The role of MetAP2 in the mitogenic activity of these cells is unknown.

scholarly journals Residues within the Foot-and-Mouth Disease Virus 3Dpol Nuclear Localization Signal Affect Polymerase Fidelity

2020 ◽  
Vol 94 (17) ◽  
Author(s):  
Anna Kloc ◽  
Devendra K. Rai ◽  
Douglas P. Gladue ◽  
Elizabeth Schafer ◽  
Mary Kenney ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Molecular Dynamics Simulation ◽  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Foot And Mouth Disease ◽  
Dynamics Simulation ◽  
Mouth Disease Virus ◽  
Localization Signal

ABSTRACT Many RNA viruses encode a proof-reading deficient, low-fidelity RNA-dependent polymerase (RdRp), which generates genetically diverse populations that can adapt to changing environments and thwart antiviral therapies. 3Dpol, the RdRp of the foot-and-mouth disease virus (FMDV), is responsible for replication of viral genomes. The 3Dpol N terminus encodes a nuclear localization signal (NLS) sequence,MRKTKLAPT, important for import of the protein to host nucleus. Previous studies showed that substitutions at residues 18 and 20 of the NLS are defective in proper incorporation of nucleotides and RNA binding. Here, we use a systematic alanine scanning mutagenesis approach to understand the role of individual residues of the NLS in nuclear localization and nucleotide incorporation activities of 3Dpol. We identify two residues of 3Dpol NLS, T19 and L21, that are important for the maintenance of enzyme fidelity. The 3Dpol NLS alanine substitutions of T19 and L21 results in aberrant incorporation of nucleoside analogs, conferring a low fidelity phenotype of the enzyme. A molecular dynamics simulation of RNA- and mutagen (RTP)-bound 3Dpol revealed that the T19 residue participates in a hydrogen bond network, including D165 in motif F and R416 at the C terminus of the FMDV 3Dpol and RNA template-primer. Based on these findings and previous studies, we conclude that at least the first six residues of theMRKTKLAPT sequence motif play a vital role in the maintenance of faithful RNA synthesis activity (fidelity) of FMDV 3Dpol, suggesting that the role of the NLS motif in similar viral polymerases needs to be revisited. IMPORTANCE In this study, we employed genetic and molecular dynamics approaches to analyze the role of individual amino acids of the FMDV 3Dpol nuclear localization signal (NLS). The NLS residues were mutated to alanine using a type A full-genome cDNA clone, and the virus progeny was analyzed for defects in growth and in competition with the parental virus. We identified two mutants in 3Dpol, T19A and L21A, that exhibited high rate of mutation, were sensitive to nucleotide analogs, and displayed reduced replicative fitness compared to the parental virus. Using molecular dynamics simulation, we demonstrated that residues T19 and L21 played a role in the structural configuration of the interaction network at the 3Dpol palm subdomain. Cumulatively, our data suggest that the T19 and L21 3Dpol amino acids are important for maintaining the fidelity of the FMDV polymerase and ensuring faithful replication of the FMDV genome.

scholarly journals D-Retro Inverso (DRI) Amylin and the Stability of Amylin Fibrils

2020 ◽  
Author(s):  
Preeti Pandey ◽  
Natalie Nguyen ◽  
Ulrich H.E. Hansmann
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Fibril Structure ◽  
Elongation Process ◽  
The Stability ◽  
Dynamics Simulations ◽  
Potential Use

AbstractMotivated by the role that amylin aggregates pay in type-II diabetes, we compare the stability of regular amylin fibrils with the stability of fibrils where L-amino acid chains are replaced by D-Retro Inverso (DRI) amylin, i.e., peptides where the sequence of amino acids is reversed, and at the same time the L-amino acids are replaced by their mirror images. Our molecular dynamics simulations show that despite leading to only marginal difference in fibril structure and stability, aggregating DRI-amylin peptides have different pattern of contacts and hydrogen bonding. Because of these differences does DRI-amylin, when interacting with regular (L) amylin, alter the elongation process and lowers the stability of hybrid amylin fibrils. Our results suggest not only a potential use of DRI-amylin as inhibitor of amylin fibril-formation, but points also to the possibility of using insertion of DRI-proteins in L-assemblies as a way to probe the role of certain kinds of hydrogen bonds in supra-molecular assemblies or aggregates.

scholarly journals The differential ability of human IgG1 and IgG4 to activate complement is determined by the COOH-terminal sequence of the CH2 domain.

1991 ◽  
Vol 173 (4) ◽  
pp. 1025-1028 ◽  
Author(s):  
M H Tao ◽  
S M Canfield ◽  
S L Morrison
Keyword(s):  
Amino Acids ◽  
Complement Activation ◽  
Terminal Sequence ◽  
Terminal Part ◽  
Chimeric Antibodies ◽  
Human Igg1 ◽  
Domain Switch ◽  
Ch2 Domain ◽  
Differential Ability

Using domain switch chimeric antibodies, we confirm the important role of CH2 in complement activation. In addition, we demonstrate that the structures responsible for the differential ability of human IgG1 and IgG4 to activate complement are located at the COOH-terminal part (from residue 292 to 340) of the CH2 domain. The amino acids in CH2 that might be involved in complement interaction are discussed. While CH3 contributes to efficient complement activation, CH3 from IgG2 and CH3 IgG3 are equally effective.

Mitochondrial matrix calcium ions regulate energy production in myocardium: A cytochemical study

1990 ◽  
Vol 48 (2) ◽  
pp. 166-167
Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet
Keyword(s):  
Energy Metabolism ◽  
Calcium Ions ◽  
Energy Production ◽  
Regulation Of Respiration ◽  
Free Calcium ◽  
Mitochondrial Matrix ◽  
Cytochemical Study ◽  
Nmr Techniques

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.

Role of amino acids and micronutrients on biosynthesis of spiramycins

1981 ◽  
Vol 31 (1) ◽  
pp. 189-193 ◽  
Author(s):  
Mohamed A. Ashy ◽  
Abd El-Galil ◽  
M. Khalil ◽  
Abou-Zeid A. Abou-Zeid
Keyword(s):  
Amino Acids
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