Search results for "specificity"

Eggshell types and their evolutionary correlation with life-history strategies in squamates

2015

The eggshell is an important physiological structure for the embryo. It enables gas exchange, physical protection and is a calcium reserve. Most squamates (lizards, snakes, worm lizards) lay parchment-shelled eggs, whereas only some gekkotan species, a subgroup of lizards, have strongly calcified eggshells. In viviparous (live-bearing) squamates the eggshell is reduced or completely missing (hereafter “shell-less”). Recent studies showed that life-history strategies of gekkotan species differ between species with parchment- and rigid-shelled eggshells. Here we test if the three different eggshell types found in the squamates are also associated with different life-history strategies. We fir…

Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes

2007

Abstract Background The melanocortin (MC) receptors have a key role in regulating body weight and pigmentation. They belong to the rhodopsin family of G protein-coupled receptors (GPCRs). The purpose of this study was to identify ancestral MC receptors in agnathan, river lamprey. Results We report cloning of two MC receptors from river lamprey. The lamprey receptors, designated MCa and MCb, showed orthology to the MC1 and MC4 receptor subtypes, respectively. The molecular clock analysis suggested that lamprey MC receptor genes were not duplicated recently and diverged from each other more than 400 MYR ago. Expression and pharmacological characterization showed that the lamprey MCa receptor …

Hepassocin as a treatment for fulminant hepatic failure: will it translate from rats to human?

2010

Acute liver failure (ALF) is defined as the abrupt loss of hepatic cellular function in a patient without pre-existing liver disease, with the subsequent development of coagulopathy, jaundice and encephalopathy. It remains one of the most challenging medical emergencies, due to the multiorgan nature of the disease, the rapid evolution of the clinical condition and the need for multidisciplinary supportive interventions in order to assess the necessity for liver transplantation (LT) correctly.1 Despite different causes of ALF, the mode of cell death typically follows one of two patterns: necrosis or apoptosis; apoptosis is manifest by nuclear and cytoplasmic shrinkage without disturbance of …

Bax inhibitor-1 is likely a pH-sensitive calcium leak channel, not a H+/Ca2+ exchanger.

2014

The endoplasmic reticulum (ER) plays a key role in the synthesis, folding, and sorting of proteins, and disturbances of this delicate system can cause cell death. The ER also serves as the major intracellular calcium (Ca(2+)) store, and release of Ca(2+) from this store controls diverse cellular functions. At the interface of both these functions of the ER is Bax inhibitor-1 (BI-1), an evolutionarily conserved multifunctional protein that mediates Ca(2+) efflux from the ER and protects against ER stress. Several mechanisms have been proposed to explain how BI-1 might mediate Ca(2+) efflux from the ER. Chang et al. present structural evidence that a bacterial homolog of BI-1, BsYetJ, is a pH…

Propeller Flaps: A Review of Indications, Technique, and Results

2014

In the last years, propeller flaps have become an appealing option for coverage of a large range of defects. Besides having a more reliable vascular pedicle than traditional flap, propeller flaps allow for great freedom in design and for wide mobilization that extend the possibility of reconstructing difficult wounds with local tissues and minimal donor-site morbidity. They also allow one-stage reconstruction of defects that usually require multiple procedures. Harvesting of a propeller flap requires accurate patient selection, preoperative planning, and dissection technique. Complication rate can be kept low, provided that potential problems are prevented, promptly recognized, and adequate…

Biochemistry and medicinal chemistry of the dengue virus protease.

2014

Inhibition of glycosaminoglycan modification of perlecan domain I by site-directed mutagenesis changes protease sensitivity and laminin-1 binding act…

1998

AbstractGlycosaminoglycan attachment to perlecan domain I (173 residues) was completely prevented by site-directed mutagenesis of Ser-65, Ser-71 and Ser-76 as shown by recombinant production in mammalian cells. This did not interfere with the proper folding of the domain's SEA module but enhanced its sensitivity to neutral proteases. Lack of substitution also abolished binding to the two major heparin binding sites of laminin-1.

Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C

2014

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad ran…

Enteroviruses and coronaviruses: similarities and therapeutic targets

2021

ABSTRACT Introduction: Enteroviruses are common viruses causing a huge number of acute and chronic infections and producing towering economic costs. Similarly, coronaviruses cause seasonal mild infections, epidemics, and even pandemics and can lead to severe respiratory symptoms. It is important to develop broadly acting antiviral molecules to efficiently tackle the infections caused by thes. Areas covered: This review illuminates the differences and similarities between enteroviruses and coronaviruses and examines the most appealing therapeutic targets to combat both virus groups. Publications of both virus groups and deposited structures discovered through PubMed to March 2021 for viral p…

Analysis of serine proteases from marine sponges by 2-D zymography.

2007

Proteolytic activities isolated from the marine demosponges Geodia cydonium and Suberites domuncula were analyzed by 2-D zymography, a technique that combines IEF and zymography. After purification, a 200 kDa proteolytically active protein band was obtained from G. cydonium when analyzed in gelatin copolymerized 1-D zymograms. The enzymatic activity was quantified using alpha-N-benzoyl-D-arginine p-nitroanilide (BAPNA) as a substrate and corresponded to a serine protease. The protease activity was resistant to urea and SDS. DTT and 2-mercaptoethanol (2-ME) did not significantly change the protease activity, but induced a shift in molecular mass of the proteolytic band to lower M(r) values a…