Self-protective responses to norvaline-induced stress in a leucyl-tRNA synthetase editing-deficient yeast strain.

The editing function of aminoacyl-tRNA synthetases (aaRSs) is indispensible for formation of the correct aminoacyl-tRNAs. Editing deficiency may lead to growth inhibition and the pathogenesis of various diseases. Herein, we confirmed that norvaline (Nva) but not isoleucine or valine is the major threat to the editing function of Saccharomyces cerevisiae leucyl-tRNA synthetase (ScLeuRS), both in vitro and in vivo.

Conotoxin αD-GeXXA utilizes a novel strategy to antagonize nicotinic acetylcholine receptors.

Nicotinic acetylcholine receptors (nAChRs) play essential roles in transmitting acetylcholine-mediated neural signals across synapses and neuromuscular junctions, and are also closely linked to various diseases and clinical conditions. Therefore, novel nAChR-specific compounds have great potential for both neuroscience research and clinical applications. Conotoxins, the peptide neurotoxins produced by cone snails, are a rich reservoir of novel ligands that target receptors, ion channels and transporters in the nervous system.

Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.

BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.

Critical effect of peptide cyclization on the potency of peptide inhibitors against Dengue virus NS2B-NS3 protease.

Dengue virus (DENV) infection is a serious public health threat worldwide that demands effective treatment. In the search for potent virus protease inhibitors, several cone snail venoms were screened against serotype 2 DENV NS2B-NS3 protease, and one conotoxin, MrIA, was identified to have inhibitory activity. The inhibitory activity was attributed to a disulfide bond-mediated loop, from which rational optimization was made to improve the potency and stability.

A helical conotoxin from Conus imperialis has a novel cysteine framework and defines a new superfamily.

Cone snail venoms are a rich source of peptides, many of which are potent and selective modulators of ion channels and receptors. Here we report the isolation and characterization of two novel conotoxins from the venom of Conus imperialis. These two toxins contain a novel cysteine framework, C-C-C-CC-C, which has not been found in other conotoxins described to date.

Purification, cDNA cloning, and recombinant expression of chymotrypsin C from porcine pancreas.

Chymotrypsin C is a bifunctional secretory-type serine protease in pancreas; besides proteolytical activity, it also exhibits a calcium-decreasing activity in serum. In this study, we purified activated chymotrypsin C from porcine pancreas, and identified its three active forms. Active chymotrypsin C was found to be different in the length of its 13-residue activation peptide due to carboxydipeptidase (present in the pancreas) degradation or autolysis of the activated chymotrypsin C itself, resulting in the removal of several C-terminus residues from the activation peptide.

A novel conotoxin, qc16a, with a unique cysteine framework and folding.

A novel conotoxin, qc16a, was identified from the venom of vermivorous Conus quercinus. qc16a has only 11 amino acid residues, DCQPCGHNVCC, with a unique cysteine pattern. Its disulfide connectivity was determined to be I-IV, II-III.

Effect of chymotrypsin C and related proteins on pancreatic cancer cell migration.

Pancreatic cancer is a malignant cancer with a high mortality rate. The amount of chymotrypsin C in pancreatic cancer cells is only 20% of that found in normal cells. Chymotrypsin C has been reported to be involved in cancer cell apoptosis, but its effect on pancreatic cancer cell migration is unclear.

Chemical synthesis and characterization of two α4/7-conotoxins.

α-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two α-conotoxins, Mr1.1 from the molluscivorous Conus marmoreus and Lp1.

Identification of neuropeptide Y-like conopeptides from the venom of Conus betulinus.

Neuropeptide Y (NPY) is a ubiquitous endocrine neuropeptide found in vertebrate and invertebrate. In our present work, two NPY-like exocrine conopeptides (designated as cono-NPYs) were first identified in the venom of cone snails. Both cono-NPYs showed sequence characteristics of invertebrate NPYs, suggesting that some exocrine venom peptides are probably evolved from the preexisting endocrine peptides during the evolution of cone snails.

A new subfamily of conotoxins belonging to the A-superfamily.

Two novel conotoxins from vermivorous cone snails Conus pulicarius and Conus tessulatus, designated as Pu14.1 and ts14a, were identified by cDNA cloning and peptide purification, respectively. The signal sequence of Pu14.

Snapshot of the interaction between HIV envelope glycoprotein 120 and protein disulfide isomerase.

The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein 120 (gp120) binds to cell surface receptors and mediates HIV entry. Previous studies suggest the cell surface protein disulfide isomerase (PDI) might interact with disulfide bond(s) of gp120 and thus facilitate HIV-1 entry. In the present study, a kinetic trapping approach was used to capture the disulfide cross-linking intermediate between gp120 and PDI.

Novel conopeptides in a form of disulfide-crosslinked dimer.

In our present work, seven conotoxins and conopeptides were cloned from four cone snail species based on the M-superfamily signal peptides. Among them, two conopeptides, Vt3.1 and Vt3.

Small peptides derived from the Lys active fragment of the mung bean trypsin inhibitor are fully active against trypsin.

The Bowman-Birk protease inhibitors have recently attracted attention for their potential as cancer preventive and suppressing agents. They contain two canonical binding loops, both consisting of nine highly conserved residues capable of inhibiting corresponding serine proteases. In this study, we cloned the cDNA of the mung bean trypsin inhibitor, one of the most studied Bowman-Birk protease inhibitors.

Two short D-Phe-containing cysteine-free conopeptides from Conus marmoreus.

The cysteine-free conopeptides are naturally occurring components of the venom of cone snails and have been relatively less investigated than the cysteine-containing conopeptides. In this work, we used thiol-exchange chromatography to isolate cysteine-free conopeptides from the venom of Conus marmoreus. The full-length previously reported conomarphin and two novel shortened forms of it were found in the cysteine-free conopeptide fraction.

Characterization of a novel alpha4/4-conotoxin, Qc1.2, from vermivorous Conus quercinus.

As part of continuing studies of the identification of gene organization and cloning of novel alpha-conotoxins, the first alpha4/4-conotoxin identified in a vermivorous Conus species, designated Qc1.2, was originally obtained by cDNA and genomic DNA cloning from Conus quercinus collected in the South China Sea. The predicted mature toxin of Qc1.

The ternary structure of the double-headed arrowhead protease inhibitor API-A complexed with two trypsins reveals a novel reactive site conformation.

The double-headed arrowhead protease inhibitors API-A and -B from the tubers of Sagittaria sagittifolia (Linn) feature two distinct reactive sites, unlike other members of their family. Although the two inhibitors have been extensively characterized, the identities of the two P1 residues in both API-A and -B remain controversial. The crystal structure of a ternary complex at 2.

New conotoxins define the novel I3-superfamily.

We purified two novel conotoxins, designated as ca11a and ca11b, from the venom of Conus caracteristicus. Based on the amino acid sequence of mature ca11a, we cloned its full-length cDNA. Based on the signal peptide of ca11a, several ca11a-like conotoxins were cloned from C.

Recombinant expression of a chitosanase and its application in chitosan oligosaccharide production.

Recently, considerable attention has been focused on chitosan oligosaccharides (COSs) due to their various biological activities. COSs can be prepared by enzymatic degradation of chitosan, which is the deacetylation product of chitin, one of the most abundant biopolymers in nature. In the current study, we recombinantly expressed a chitosanase and used it for COS preparation.

Structure-function relationship of bifunctional scorpion toxin BmBKTx1.

As the first identified scorpion toxin active on both big conductance Ca2+-activated K+ channels (BK) and small conductance Ca2+-activated K+ channels (SK), BmBKTx1 has been proposed to have two separate functional faces for two targets. To investigate this hypothesis, two double mutants, K21A-Y30A and R9A-K11A, together with wild-type toxin were expressed in Escherichia coli. The recombinant toxins were tested on cockroach BK and rat SK2 channel for functional assay.

Design of peptide inhibitors for furin based on the C-terminal fragment of histone H1.2.

The mammalian proprotein convertase furin has been found to play an important role in diverse physiological and pathological events, such as the activation of viral glycoproteins and bacterial exotoxins. Small, non-toxic and highly active, furin inhibitors are considered to be attractive drug candidates for diseases caused by virus and bacteria. In this study, a series of peptide inhibitors were designed and synthesized based on the C-terminal fragment of histone H1.

alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nicotinic acetylcholine receptors.

Cone snails comprise approximately 700 species of venomous molluscs which have evolved the ability to generate multiple toxins with varied and exquisite selectivity. alpha-Conotoxin is a powerful tool for defining the composition and function of nicotinic acetylcholine receptors which play a crucial role in excitatory neurotransmission and are important targets for drugs and insecticides. An alpha4/7 conotoxin, Lp1.

Isolation and cloning of a conotoxin with a novel cysteine pattern from Conus caracteristicus.

A new conotoxin, ca16a, containing 8 cysteine residues was purified, sequenced, and cloned from a worm-hunting snail, Conus caracteristicus. This conotoxin is an extremely hydrophilic peptide comprising 34 residues, with 4 acidic and 4 basic residues. It is rich in polar Gly, Ser, and Thr residues and includes a hydroxylated Pro residue.

Interaction of Mint3 with Furin regulates the localization of Furin in the trans-Golgi network.

Furin is a proprotein convertase that cycles between the plasma membrane, endosomes and the trans-Golgi network (TGN), maintaining a predominant distribution in the latter. Mint3, a member of the Mint protein family, is involved in the signaling and trafficking of membrane proteins. Until now, little has been known about the roles of Mint3 in the localization or trafficking of Furin.

mr1e, a conotoxin from Conus marmoreus with a novel disulfide pattern.

Conotoxins are well known for their highly variable structures and functions. Here we report the identification of a novel conotoxin named mr1e from Conus marmoreus. mr1e is composed of 11 amino acid residues cross-linked by two disulfide bonds (CCHSSWCKHLC).