00597nas a2200169 4500008004100000022001400041245008000055210006900135260000800204300000900212490000700221653002300228653002100251100002000272700002800292856010700320 2014 eng d a2053-273300aStructural characterization of a UbiA superfamily member of archaeal origin0 aStructural characterization of a UbiA superfamily member of arch cMAR aC4010 v7010aLipid biosynthesis10aUbiA superfamily1 aBoral, Debjyoti1 aRamasamy, Suresh, Kumar uhttps://library.ncl.res.in/content/structural-characterization-ubia-superfamily-member-archaeal-origin01801nas a2200265 4500008004100000022001400041245007700055210006900132260000800201300001100209490000800220520092900228653002201157653001401179653002501193653002901218653002401247653001601271100002901287700002801316700002001344700002601364700003601390856010901426 2019 eng d a0003-986100aBaicalein suppresses repeat tau fibrillization by sequestering oligomers0 aBaicalein suppresses repeat tau fibrillization by sequestering o cOCT a1081190 v6753 a

Alzheimer's disease (AD) is a neurodegenerative disorder caused by protein misfolding, aggregation and accumulation in the brain. A large number of molecules are being screened against these pathogenic proteins but the focus for therapeutics is shifting towards the natural compounds as aggregation inhibitors, mainly due to their minimum adverse effects. Baicalein is a natural compound belonging to the class of flavonoids isolated from the Chinese herb Scutellaria baicalensis. Here we applied fluorescence, absorbance, microscopy, MALDI-TOF spectrophotometry and other biochemical techniques to investigate the interaction between Tau and Baicalein in vitro. We found the aggregation inhibitory properties of Baicalein for the repeat Tau. Overall, the potential of Baicalein in dissolving the preformed Tau oligomers as well as mature fibrils can be of utmost importance in therapeutics for Alzheimer's disease.

10aAlzheimer disease10aBaicalein10aMicrotubule assembly10aPaired helical filaments10aProtein aggregation10atau protein1 aSonawane, Shweta, Kishor1 aBalmik, Abhishek, Ankur1 aBoral, Debjyoti1 aRamasamy, Sureshkumar1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/baicalein-suppresses-repeat-tau-fibrillization-sequestering-oligomers01757nas a2200157 4500008004100000245009000041210006900131260000800200300001400208490000700222520118200229100002001411700003001431700002601461856011201487 2019 eng d00aStructural insight into a membrane intrinsic Acyltransferase from Chlorobium tepidum 0 aStructural insight into a membrane intrinsic Acyltransferase fro cNOV a1290-12970 v763 a

The Lipid A component of the outer membrane of Gram-negative bacteria is an integral part of the permeability barrier known as LPS, which actively prevents the uptake of bactericidal compounds. It is clinically very significant, as it is known to elicit a strong immune response in the humans, through the TLR4 complex. The Lipid A species are synthesized through a highly conserved multistep biosynthetic pathway. The final step is catalyzed by acyltransferases of the HtrB/MsbB family, which are members of a superfamily of enzymes, present in all domains of life with important roles to play in various biological processes. The investigation of a putative dual functioning enzyme which can add both laurate and myristate residues to the (Kdo)(2)-lipid IVA (precursor of Lipid A) would give a snapshot into the versatility of substrates that these enzymes catalyze. In this study we have cloned and purified to homogeneity, such a putative dual functional acyltransferase from Chlorobium tepidum, and attempted to study the enzyme in more details in terms of its sequence and structural aspects, as it lacks conserved residues with other enzymes of the same family.

1 aBoral, Debjyoti1 aVankudoth, Koteswara, Rao1 aRamasamy, Sureshkumar uhttps://library.ncl.res.in/content/structural-insight-membrane-intrinsic-acyltransferase-chlorobium-tepidum02373nas a2200241 4500008004100000022001400041245013900055210006900194260000800263300001200271490000700283520152500290653001901815653002001834653001101854653002101865653002001886653002101906100002001927700003001947700002601977856012802003 2020 eng d a0929-866500aArcheal Di-O-geranylgeranyl glyceryl phosphate synthase of a UbiA superfamily member provides insight into the multiple human diseases0 aArcheal DiOgeranylgeranyl glyceryl phosphate synthase of a UbiA  cJAN a568-5730 v273 a

One of the unique characteristic features of the domain archaea, are the lipids that form the hydrophobic core of their cell membrane. These membrane lipids are characterized by distinctive isoprenoid biochemistry and the building blocks are two core lipid structures, sn-2,3-diphytanyl glycerol diether (archaeol) and sn-2,3-dibiphytanyl diglycerol tetraether (caldarchaeol). Archaeol has two phytanyl chains (C-20 in a bilayer structure connected to the glycerol moiety by an ether bond. The enzyme involved in this bilayer formation is Di-O-Geranylgeranyl Glyceryl Phosphate Synthase (DGGGPS), which is a member of a very versatile superfamily of enzymes known as UbiA superfamily. Multiple sequence analysis of the typical members of the UbiA superfamily indicates that the majority of conserved residues are located around the central cavity of these enzymes. Interestingly few of these conserved residues in the human homologs are centrally implicated in several human diseases, on basis of the major mutations reported against these diseases in the earlier clinical studies. It remains to he investigated about the role of these conserved residues in the biochemistiy of these enzymes. The binding and active site of these enzymes found to be similar architecture but have different substrate affinities ranging from aromatic to linear compounds. So further investigation of UbiA superfamily may be translated to novel therapeutic and diagnostic application of these proteins in human disease management.

10aArcheal lipids10abiA superfamily10aDGGGPS10agenetic diseases10alipid synthesis10amembrane protein1 aBoral, Debjyoti1 aRao, Vamkudoth, Koteswara1 aRamasamy, Sureshkumar uhttps://library.ncl.res.in/content/archeal-di-o-geranylgeranyl-glyceryl-phosphate-synthase-ubia-superfamily-member-provides01662nas a2200241 4500008004100000022001400041245006200055210006200117260000800179300001000187490000700197520088100204100002901085700003401114700002001148700002801168700002801196700001601224700002601240700002601266700003601292856009201328 2020 eng d a2045-232200aEGCG impedes human Tau aggregation and interacts with Tau0 aEGCG impedes human Tau aggregation and interacts with Tau cJUL a125790 v103 a

Tau aggregation and accumulation is a key event in the pathogenesis of Alzheimer's disease. Inhibition of Tau aggregation is therefore a potential therapeutic strategy to ameliorate the disease. Phytochemicals are being highlighted as potential aggregation inhibitors. Epigallocatechin-3-gallate (EGCG) is an active phytochemical of green tea that has shown its potency against various diseases including aggregation inhibition of repeat Tau. The potency of EGCG in altering the PHF assembly of full-length human Tau has not been fully explored. By various biophysical and biochemical analyses like ThS fluorescence assay, MALDI-TOF analysis and Isothermal Titration Calorimetry, we demonstrate dual effect of EGCG on aggregation inhibition and disassembly of full-length Tau and their binding affinity. The IC50 for Tau aggregation by EGCG was found to be 64.2 mu M.

1 aSonawane, Shweta, Kishor1 aChidambaram, Hariharakrishnan1 aBoral, Debjyoti1 aGorantla, Nalini, Vijay1 aBalmik, Abhishek, Ankur1 aDangi, Abha1 aRamasamy, Sureshkumar1 aMarelli, Udaya, Kiran1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/egcg-impedes-human-tau-aggregation-and-interacts-tau