116 research outputs found
Alu insertion/deletion of ACE gene polymorphism might not affect significantly the serum bradykinin level in hypertensive patients taking ACE inhibitors
Background Angiotensin I-converting enzyme (ACE) has two homologous catalytic domains, the N- and C-domains. Our previous study suggested that Alu insertion (I allele) in the intron 16 of ACE resulted in premature codon termination. The I allele has only one active site in the N-domain while the Alu deletion (D allele) still has two active sites of ACE. Therefore the effect of I/D polymorphism of ACE on the enzyme's ability to catalyse bradykinin is still not widely known. Aims This study aimed to examine the serum bradykinin level in hypertensive patients with I/D polymorphism of ACE, who were treated with ACE inhibitor. Subjects and methods The serum bradykinin and I/D polymorphism have been detected in 64 hypertensive patients taking ACE inhibitor (lisinopril or captopril) for at least eight weeks with good medication adherence. The binding affinity of ACE with its receptor was calculated by molecular docking. Results The findings show that genotype II is more frequent in the population the researchers observed (53.12%) compared to ID (23.44%) and DD (23.44%) variances. On the other hand, the bradykinin level is not affected by genotype of the ACE genes on the population. Bradykinin increases in patients with genotype II who are given captopril, but decreases in patients treated with lisinopril. Nevertheless, there is no statistically significant difference. Conclusion This study suggests that the polymorphism might not significantly affect the serum bradykinin level in hypertensive patients taking ACE inhibitors
Crystal and Molecular Structure and DFT Calculations of the Steroidal Oxime 6E-Hydroximino-androst-4-ene-3,17-dione (C<sub>19</sub>H<sub>25</sub>NO<sub>3</sub>) a Molecule with Antiproliferative Activity
The single crystal X-ray structure of the novel steroid derivative, 6E-hydroximino-androst-4-ene-3,17-dione ( C19H25NO3) (code name RB-499), possessing antiproliferative activity against various cell lines is presented.
The analysis produced the following results: chemical formula C19H25NO3; Mr = 315.40; crystals are orthorhombic space group P212121 with Z = 4 molecules per unit cell with a = 6.2609(2), b = 12.5711(4), c = 20.0517(4) Å,Vc = 1578.18(7) Å3, crystal density Dc = 1.327 g/cm³. Structure determination was performed by direct methods, Fourier and full-matrix least-squares refinement. Hydrogens were located in the electron density and refined in position with isotropic thermal parameters.
The final R-index was 0.0324for 3140 reflections with I > 2σ and 308 parameters. The Absolute Structure Parameter − 0.07(5) confirms the correct allocation of the absolute configuration. The presence of the double bond C=O at position 3 in Ring A has caused a distortion from the usual chair conformation and created an unusual distorted sofa conformation folded across an approximate m-plane through C(1)–C(4). Ring B is a distorted chair, its conformation being influenced by the presence of the C(6)=N(6)–O(6)H group in position 6. Ring C is a symmetrical chair. Ring D exhibits both a distorted mirror symmetry conformation [influenced by the C(17)=O(17) group] and a distorted twofold conformation. DFT calculations indicated some degree of flexibility in rings A, C and D with ring A showing the greatest variation in torsion angles. The crystal packing is governed by H-bonds involving O(3), O(6) and O(17). DFT calculations of bond distances and angles, optimized at the B3LYP/6–31++G(d,p) level, were in good agreement with the X-ray structure
Ultra-high resolution X-ray structures of two forms of human recombinant insulin at 100 K
The crystal structure of a commercially available form of human recombinant (HR) insulin, Insugen (I), used in the treatment of diabetes has been determined to 0.92 Å resolution using low temperature, 100 K, synchrotron X-ray data collected at 16,000 keV (λ = 0.77 Å). Refinement carried out with anisotropic displacement parameters, removal of main-chain stereochemical restraints, inclusion of H atoms in calculated positions, and 220 water molecules, converged to a final value of R = 0.1112 and Rfree = 0.1466. The structure includes what is thought to be an ordered propanol molecule (POL) only in chain D(4) and a solvated acetate molecule (ACT) coordinated to the Zn atom only in chain B(2). Possible origins and consequences of the propanol and acetate molecules are discussed. Three types of amino acid representation in the electron density are examined in detail: (i) sharp with very clearly resolved features; (ii) well resolved but clearly divided into two conformations which are well behaved in the refinement, both having high quality geometry; (iii) poor density and difficult or impossible to model. An example of type (ii) is observed for the intra-chain disulphide bridge in chain C(3) between Sγ6–Sγ11 which has two clear conformations with relative refined occupancies of 0.8 and 0.2, respectively. In contrast the corresponding S–S bridge in chain A(1) shows one clearly defined conformation. A molecular dynamics study has provided a rational explanation of this difference between chains A and C. More generally, differences in the electron density features between corresponding residues in chains A and C and chains B and D is a common observation in the Insugen (I) structure and these effects are discussed in detail. The crystal structure, also at 0.92 Å and 100 K, of a second commercially available form of human recombinant insulin, Intergen (II), deposited in the Protein Data Bank as 3W7Y which remains otherwise unpublished is compared here with the Insugen (I) structure. In the Intergen (II) structure there is no solvated propanol or acetate molecule. The electron density of Intergen (II), however, does also exhibit the three types of amino acid representations as in Insugen (I). These effects do not necessarily correspond between chains A and C or chains B and D in Intergen (II), or between corresponding residues in Insugen (I).
The results of this comparison are reported
How do mutations and allosteric inhibitors modulate caspase-7 activity? A molecular dynamics study
Investigation of binding properties of two ethidium derivatives with serum albumins: spectral and computational approach
The possible effect of microRNA-155 (miR-155) and BACE1 inhibitors in the memory of patients with down syndrome and Alzheimer's disease: Design, synthesis, virtual screening, molecular modeling and biological evaluations
Energy-based automatic determination of buffer region in the divide-and-conquer second-order Moller-Plesset perturbation theory
In the linear-scaling divide-and-conquer (DC) electronic structure method, each subsystem is calculated together with the neighboring buffer region, the size of which affects the energy error introduced by the fragmentation in the DC method. The DC self-consistent field calculation utilizes a scheme to automatically determine the appropriate buffer region that is as compact as possible for reducing the computational time while maintaining acceptable accuracy (J. Comput. Chem. 2018, 39, 909). To extend the automatic determination scheme of the buffer region to the DC second-order Moller-Plesset perturbation (MP2) calculation, a scheme for estimating the subsystem MP2 correlation energy contribution from each atom in the buffer region is proposed. The estimation is based on the atomic orbital Laplace MP2 formalism. Based on this, an automatic buffer determination scheme for the DC-MP2 calculation is constructed and its performance for several types of systems is assessed
Energy‐based automatic determination of buffer region in the divide‐and‐conquer second‐order Møller–Plesset
- …