Crystal structure of the jacalin-T-antigen complex and a comparative study of lectin-T-antigen complexes

Thomsen-Friedenreich antigen (Galβ1-3GalNAc), generally known as T-antigen, is expressed in more than 85% of human carcinomas. Therefore, proteins which specifically bind T-antigen have potential diagnostic value. Jacalin, a lectin from jack fruit (Artocarpus integrifolia) seeds, is a tetramer of molecular mass 66 kDa. It is one of the very few proteins which are known to bind T-antigen. The crystal structure of the jacalin-T-antigen complex has been determined at 1.62 Å resolution. The interactions of the disaccharide at the binding site are predominantly through the GalNAc moiety, with Gal interacting only through water molecules. They include a hydrogen bond between the anomeric oxygen of GalNAc and the π electrons of an aromatic side-chain. Several intermolecular interactions involving the bound carbohydrate contribute to the stability of the crystal structure. The present structure, along with that of the Me-α-Gal complex, provides a reasonable qualitative explanation for the known affinities of jacalin to different carbohydrate ligands and a plausible model of the binding of the lectin to T-antigen O-linked to seryl or threonyl residues. Including the present one, the structures of five lectin-T-antigen complexes are available. GalNAc occupies the primary binding site in three of them, while Gal occupies the site in two. The choice appears to be related to the ability of the lectin to bind sialylated sugars. In either case, most of the lectin-disaccharide interactions are at the primary binding site. The conformation of T-antigen in the five complexes is nearly the same

3-D struktura serumske paraoksonaze 1 objašnjava njezinu aktivnost, stabilnost, topljivost i kristalizaciju

Serum paraoxonases (PONs) exhibit a wide range of physiologically important hydrolytic activities, including drug metabolism and detoxification of nerve gases. PON1 and PON3 reside on high-density lipoprotein (HDL) (the “good cholesterol”), and are involved in the alleviation of atherosclerosis. Members of the PON family have been identified not only in mammals and other vertebrates, but also in invertebrates. We earlier described the first crystal structure of a PON family member, a directly-evolved variant of PON1, at 2.2 Å resolution. PON1 is a 6-bladed beta-propeller with a unique active-site lid which is also involved in binding to HDL. The 3-D structure, taken together with directed evolution studies, permitted analysis of mutations which enhanced the stability, solubility and crystallizability of this PON1 variant. The structure permits a detailed description of PON1’s active site and suggests possible mechanisms for its catalytic activity on certain substrates.Serumske paraoksonaze (PONs) imaju široki raspon fiziološki važnih hidrolitičkih aktivnosti uključujući metabolizam lijekova i detoksikaciju nervnih plinova. PON1 i PON3 smještene su na lipoproteinima visoke gustoće (engl. high-density lipoprotein; HDL - “dobri kolesterol”) i uključene su u ublažavanje ateroskleroze. Članovi skupine PON identificirani su ne samo u sisavaca i drugih kralježnjaka već i kod beskralješnjaka. Prije smo opisali prvu kristalnu strukturu člana PON skupine, direktno razrađenu varijantu PON1 pri rezoluciji 2,2 Å. PON1 je beta-propeler sa šest lopatica s jedinstvenim poklopcem aktivnog mjesta, koji je tako|er uključen u vezanje na HDL. 3-D struktura, gledana zajedno s direktnim razvojnim istraživanjima, omogućila je analizu mutacija koje povećavaju stabilnost, topljivost i kristalizaciju te PON1 varijante. Struktura dopušta detaljan opis aktivnog mjesta PON1 i sugerira moguće mehanizme za njezinu katalitičku aktivnost prema odre|enim supstratima

Microsatellite DNA Analysis of Giant Freshwater Prawn (Macrobrachium rosenbergii) from India

Giant freshwater prawn (Macrobrachium rosenbergii), a commercially important crustacean species, is widely distributed across the Indo-Pacific region. Genetic diversity of this species from five different rivers (Krishna, Mahanadi, Hooghly, Narmada and Kalu) of India was investigated using 5 polymorphic microsatellite loci. The number of alleles across loci varied from 4 to 9. The mean expected and observed heterozygosity at all loci was 0.8359 and 0.5747 respectively. Most of the loci deviated significantly from Hardy-Weinberg expectations across all the populations. Pairwise FST estimates (0.0420 to 0.0841) revealed a significant genetic structure among M. rosenbergii populations of Indian rivers. The highest (0.5140) genetic distance was observed between Krishna and Kalu populations. All five wild populations exhibited significant variation across all five microsatellite loci. The results revealed in the study will be useful for breeding programs and conservation management of this species

Mechanistic investigation of asymmetric aminohydroxylation of alkenes^†

161-168Transfer of nitrogen and oxygen in asymmetric aminohydroxylation (AA) has been examined. Electronic as well as steric effect on the nature of oxidizing agent and nitrogen source affect chemo, regio and stereoselectivity in AA reaction. A three cycle mechanistic pathway has been proposed. Results have been rationalized through an addition of alkene to Os=N bond in a [2+2] cycloaddition manner

Novel method for the preparation of tricyclic [6:6:5] systems by reductive cyclisation with LAH^†

297-299Several tricyclic [6:6:5] and [6 :7:5] systems 2a-f have been synthesized from the corresponding amido esters 1a-f. The possible mechanistic pathways have been suggested for the LAH reduction of 1a-f and are based on the products distribution

Novel euglycemic and hypolipidemic agents: Pyridine containing unsaturated thiazolidinediones

403-406Pyridyl containing 2,4-thiazolidinediones having cyclic amine as linker have been synthesized. Both unsaturated thiazolidinedione <span style="font-size:15.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:="" "times="" roman";mso-ansi-language:en-us;mso-fareast-language:en-us;="" mso-bidi-language:ar-sa"="">6<span style="font-size:15.5pt;mso-bidi-font-size: 8.5pt;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"=""> and saturated thiazolidinedione 5 and their various salts have been evaluated in db/db mice for euglycemic and hypolipidemic effects. The maleate salt of TZD 6a is found to be a very potent euglycemic and hypolipidemic compound.</span

<span style="font-size:12.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-ansi-language: EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:AR-SA" lang="EN-IN">Glucopyranosyl derivatives of 4-aminoquinoline and 2-methylimidazo[1,2-<i style="mso-bidi-font-style: normal">α</i>]-pyridine as potent reversible proton pump inhibitors^†</span>

635-638Amongst a number of 4-aminoquinoline and 2-methylimidazo[1,2,-a]-pyridine derivatives examined 2-[3-butyryl-4-(2-methylphenylamino)quinoline-8-yloxy]ethyl  2,3,4,6-tetra-<i style="mso-bidi-font-style: normal">O-acetyl<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:hiddenhorzocr;mso-ansi-language:en-in;="" mso-fareast-language:en-in;mso-bidi-language:ar-sa"="" lang="EN-IN">-β-D-glucopyranoside and 3-ethoxycarbonyl-2-methylimidazo[1,2-α]pyridine-8-yl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside have been found to be good reversible proton pump inhibitors.</span

Microsatellite DNA Analysis of Giant Freshwater Prawn (Macrobrachium rosenbergii) from India

Giant freshwater prawn (Macrobrachium rosenbergii), a commercially important crustacean species, is widely distributed across the Indo-Pacific region. Genetic diversity of this species from five different rivers (Krishna, Mahanadi, Hooghly, Narmada and Kalu) of India was investigated using 5 polymorphic microsatellite loci. The number of alleles across loci varied from 4 to 9. The mean expected and observed heterozygosity at all loci was 0.8359 and 0.5747 respectively. Most of the loci deviated significantly from Hardy-Weinberg expectations across all the populations. Pairwise FST estimates (0.0420 to 0.0841) revealed a significant genetic structure among M. rosenbergii populations of Indian rivers. The highest (0.5140) genetic distance was observed between Krishna and Kalu populations. All five wild populations exhibited significant variation across all five microsatellite loci. The results revealed in the study will be useful for breeding programs and conservation management of this species

Crystal Structure of the Jacalin–T-antigen Complex and a Comparative Study of Lectin–T-antigen Complexes

Thomsen–Friedenreich antigen (Galbeta1–3GalNAc), generally known as T-antigen, is expressed in more than 85% of human carcinomas. Therefore, proteins which specifically bind T-antigen have potential diagnostic value. Jacalin, a lectin from jack fruit (Artocarpus integrifolia ) seeds, is a tetramer of molecular mass 66 kDa. It is one of the very few proteins which are known to bind T-antigen. The crystal structure of the jacalin–T-antigen complex has been determined at 1.62 A° resolution. The interactions of the disaccharide at the binding site are predominantly through the GalNAc moiety, with Gal interacting only through water molecules. They include a hydrogen bond between the anomeric oxygen of GalNAc and the pie electrons of an aromatic side-chain. Several intermolecular interactions involving the bound carbohydrate contribute to the stability of the crystal structure. The present structure, along with that of the Me-alpha-Gal complex, provides a reasonable qualitative explanation for the known affinities of jacalin to different carbohydrate ligands and a plausible model of the binding of the lectin to T-antigen O-linked to seryl or threonyl residues. Including the present one, the structures of five lectin–T-antigen complexes are available. GalNAc occupies the primary binding site in three of them, while Gal occupies the site in two. The choice appears to be related to the ability of the lectin to bind sialylated sugars. In either case, most of the lectin–disaccharide interactions are at the primary binding site. The conformation of T-antigen in the five complexes is nearly the same

Structural and low temperature transport properties of Fe2B and FeB systems at high pressure

The evolution of crystal structure and the ground state properties of Fe2B and FeB have been studied by performing high pressure X-ray diffraction up to a pressure of ∼24 GPa and temperature dependent (4.2–300 K range) high-pressure resistivity measurements up to ∼ 2 GPa. While a pressure induced reversible structural phase transition from tetragonal to orthorhombic structure is observed at ∼6.3 GPa in Fe2B, FeB has been found to be stable in its orthorhombic phase up to the pressure of 24 GPa. In the case of Fe2B, both parent and daughter phases coexist beyond the transition pressure. The bulk modulus of FeB and Fe2B (tetragonal) have been found to be 248 GPa and 235 GPa respectively. First principle electronic structure calculations have been performed using the present experimental inputs and the calculated ground state properties agree quite well with the major findings of the experiments. Debye temperature extracted from the analysis of low temperature resistivity data is observed to decrease with pressure indicating softening of phonons in both the systems