Track topics on Twitter Track topics that are important to you
Procathepsins are inactive, immature form of cathepsins, predominantly cysteine proteases present in extracellular matrix (ECM) and in lysosomes that play a key role in a various biological processes such as bone resorption or intracellular proteolysis. Enzymatic activity of 1cathepsins can be mediated by glycosaminoglycans (GAGs) - long unbranched periodic negatively charged polysaccharides found in ECM that take part in many biological processes such as anticoagulation, angiogenesis and tissue regeneration. In addition to the known effects on mature cathepsins, GAGs can mediate maturation process of procathepsins, in particular procathepsin B. However, the detailed mechanism of this mediation at the molecular level is still unknown. In this study, for the first time aimed to unravel the role of GAGs in this process using computational approaches. We rigorously analysed procathepsin B-GAG complexes in terms of their dynamics, energetics and potential allosteric regulation. We revealed that GAGs can stabilize the conformation of procathepsin B structure with the active site accessible for the substrate, and concluded that GAGs most probably bind to the procathepsin B once the zymogen adopts the enzymatically active conformation. Our data provided a novel mechanistic view on the maturation process of procathepsin B, while the elaborated here approaches might be useful to study other procathepsins. Furthermore, our data can serve as a rational guide for experimental work on procathepsin-GAG systems that were not characterized in vivo and in vitro yet.
This article was published in the following journal.
Name: Journal of chemical information and modeling
The role and molecular mechanism of long non-coding RNA (lncRNA)-related pathways in silicosis have not been elucidated clearly. The aims of this study were to evaluate the expression of lncRNAs durin...
Glycosaminoglycans (GAGs) are involved in the pathogenesis of several urologic chronic diseases. Thus, GAGs replenishment therapy is widely reported as a therapeutic tool for chronic pelvic pain (CPP)...
Notoginsenoside R1 (NG-R1) exhibits a pharmacological activity against excessive inflammation. Here, we aimed to ascertain the anti-inflammatory role of NG-R1 in ankylosing spondylitis (AS) as well as...
The integrated maturation theory describes psychosocial, adult role, and identity maturation as interrelated domains associated with criminal desistance, but to this point these domains have not been ...
RNA-binding properties of nucleolin play a fundamental role in regulating cell growth and proliferation. We have previously shown that nucleolin plays an important regulatory role in the phenotypic tr...
Mucopolysaccharidosis (MPS) are a group of inherited, metabolic diseases caused by a deficiency of lysosomal enzymes that degrade glycosaminoglycans (GAGs). Loss of their activity results ...
Introduction Arteriovenous fistula (AVF) is the preferred hemodialysis vascular access due to its higher patency and lower infection rate. However, its major weakness is suboptimal maturat...
Sepsis is the most common cause of death in the clinical critically ill patients. We have successfully screened the sepsis biomarkers by clinical proteomics approach and found that Vimenti...
Maturity level of dendritic cells (DC) plays a pivotal role in initiating and regulating autoimmunity. In Graves' disease (GD), DCs have more active immune responses than those in healthy ...
The surgical formation of an AVF offers a unique example of vascular remodelling and adaption. Yet, the specific factors which elicit remodelling events which determine successful maturati...
Models connecting initiating events at the cellular and molecular level to population-wide impacts. Computational models may be at levels relating toxicology to adverse effects.
Protein kinase that drives both the mitotic and meiotic cycles in all eukaryotic organisms. In meiosis it induces immature oocytes to undergo meiotic maturation. In mitosis it has a role in the G2/M phase transition. Once activated by CYCLINS; MPF directly phosphorylates some of the proteins involved in nuclear envelope breakdown, chromosome condensation, spindle assembly, and the degradation of cyclins. The catalytic subunit of MPF is PROTEIN P34CDC2.
A factor identified in the brain that influences the growth and differentiation of NEURONS and NEUROGLIA. Glia maturation factor beta is the 17-kDa polypeptide product of the GMFB gene and is the principal component of GLIA MATURATION FACTOR.
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to MOLECULAR BIOLOGY and areas of computer-based techniques for solving biological problems including manipulation of models and datasets.
A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...