Structural quality assessment of different cellulosic jute fibres by X-ray diffraction

65-71The structural quality assessment of different genetically modified cellulosic jute fibres has been done by non-destructive X-ray diffraction methods to rationalize an approach for quality control of jute fibres. The results show the variations in the quality of the X-ray diffraction patterns that attribute to the characteristics of the structural/organizational properties of the jute fibre

Structural insight to mutated Y116S transthyretin by molecular dynamics simulation

197-202Familial amyloidotic polyneuropathy (FAP) is strictly associated with point mutations of transthyretin (TTR) protein. The Tyr116->Ser (Y116S) mutant TTR is an important amyloidogenic variant responsible for FAP. Structural dynamics of monomeric TTR and its mutant (Y116S) may give some clue relating to amyloid formation. In this study, molecular dynamic simulation at 310 K has been performed on wild-type and mutant (Y116S) TTR monomer, which can provide the molecular insight of structural transition in the inner and outer strand of the protein. Results show that mutation in the H-strand (Tyr116->Ser) leads to disruption of secondary structure and H-bonding pattern of some important parts of the inner DAGH-sheet of the protein. Especially, the residues T106, A108, L110 of G-strand, S117 and T119 of H-strand are affected, which are involved in the binding of thyroxin hormone. This unfolding of mutant structure during dynamics may cause instability in the protein and thus induce amyloidgenesis

p53 dependent apoptotic cell death induces embryonic malformation in Carassius auratus under chronic hypoxia.

Hypoxia is a global phenomenon affecting recruitment as well as the embryonic development of aquatic fauna. The present study depicts hypoxia induced disruption of the intrinsic pathway of programmed cell death (PCD), leading to embryonic malformation in the goldfish, Carrasius auratus. Constant hypoxia induced the early expression of pro-apoptotic/tumor suppressor p53 and concomitant expression of the cell death molecule, caspase-3, leading to high level of DNA damage and cell death in hypoxic embryos, as compared to normoxic ones. As a result, the former showed delayed 4 and 64 celled stages and a delay in appearance of epiboly stage. Expression of p53 efficiently switched off expression of the anti-apoptotic Bcl-2 during the initial 12 hours post fertilization (hpf) and caused embryonic cell death. However, after 12 hours, simultaneous downregulation of p53 and Caspase-3 and exponential increase of Bcl-2, caused uncontrolled cell proliferation and prevented essential programmed cell death (PCD), ultimately resulting in significant (p<0.05) embryonic malformation up to 144 hpf. Evidences suggest that uncontrolled cell proliferation after 12 hpf may have been due to downregulation of p53 abundance, which in turn has an influence on upregulation of anti-apoptotic Bcl-2. Therefore, we have been able to show for the first time and propose that hypoxia induced downregulation of p53 beyond 12 hpf, disrupts PCD and leads to failure in normal differentiation, causing malformation in gold fish embryos

Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease

The role of invariant water molecules in the activity of plant cysteine protease is ubiquitous in nature. On analysing the 11 different Protein DataBank (PDB) structures of plant thiol proteases, the two invariant water molecules W I and W2 (W220 and W222 in the template 1PPN structure) were observed to form H-bonds with the Ob atom of Asn 175. Extensive energy minimization and molecular dynamics simulation studies up to 2 ns on all the PDB and solvated structures clearly revealed the involvement of the H-bonding association of the two water molecules in fixing the orientation of the asparagine residue of the catalytic triad. From this study, it is suggested that H-bonding of the water molecule at the W1 invariant site better stabilizes the Asn residue at the active site of the catalytic triad

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Not AvailableDiel cyclic hypoxia occurs with varying frequency and duration in freshwater habitats, yet little is known about its effects on reproduction of freshwater fishes. The present study shows that long-term exposure of goldfish (Carassius auratus) to cyclic hypoxia (0.8 ± 0.2 mg/l dissolved oxygen) for 9 h or more, per day, altered plasma lipid and sex steroid profiles, which in turn directly or indirectly suppressed ovarian growth and viable spermatozoa production. Hypoxia decreased total cholesterol and high density lipoprotein (HDL p < 0.05) and elevated triglycerides (TG; p < 0.05) in both sexes. Plasma steroid concentrations particularly of 17α-hydroxyprogesterone (17-HP), estradiol (E2), testosterone (T) in females, and T and 11-ketotestosterone (11-KT) in males were attenuated under diel hypoxic conditions. Intriguingly, both diel and continuous hypoxia elevated plasma E2 and vitellogenin levels in males. However, neither lipid nor steroid profiles recorded any variation in a dose-dependent manner in response to diel hypoxia. The reduced GSI, decreased number of tertiary oocytes, and motile spermatozoa in hypoxic fish clearly indicate suppression of gametogenesis. Thereby, prolonged diel cyclic hypoxia may affect valuable fishery resources and fish population structure by impairing reproductive performances and inducing estrogenic effects in males.Not Availabl

KRAS Switch Mutants D33E and A59G Crystallize in the State 1 Conformation

KRAS switch loop movements play a crucial role in regulating RAS signaling, and alteration of these sensitive dynamics is a principal mechanism through which disease-associated RAS mutations lead to aberrant RAS activation. Prior studies suggest that despite a high degree of sequence similarity, the switches in KRAS are more dynamic than those in HRAS. We determined X-ray crystal structures of the rare tumorigenic KRAS mutants KRAS^D33E, in switch 1 (SW1), and KRAS^A59G, in switch 2 (SW2), bound to GDP and found these adopt nearly identical, open SW1 conformations as well as altered SW2 conformations. KRAS^A59G bound to a GTP analogue crystallizes in the same conformation. This open conformation is consistent with the inactive “state 1” previously observed for HRAS bound to GTP. For KRAS^A59G, switch rearrangements may be regulated by increased flexibility in the ⁵⁷DXXGQ⁶¹ motif at codon 59. However, loss of interactions between side chains at codons 33 and 35 in the SW1 ³³DPT³⁵ motif drives changes for KRAS^D33E. The ³³DPT³⁵ motif is conserved for multiple members of the RAS subfamily but is not found in RAB, RHO, ARF, or Gα families, suggesting that dynamics mediated by this motif may be important for determining the selectivity of RAS–effector interactions. Biochemically, the consequence of altered switch dynamics is the same, showing impaired interaction with the guanine exchange factor SOS and loss of GAP-dependent GTPase activity. However, interactions with the RBD of RAF are preserved. Overall, these observations add to a body of evidence suggesting that HRAS and KRAS show meaningful differences in functionality stemming from differential protein dynamics independent of the hypervariable region

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : Understanding the basis of differential inhibition and the role of water

<p>Abstract</p> <p>Background</p> <p>This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition.</p> <p>Results</p> <p>The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S₂-P₂ and S₃-P₃ pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition.</p> <p>Conclusion</p> <p>The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (P_n...H₂O....S_n) of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.</p