Serpins. Medical search. Frequent questions

Serpin polymerisation not only reduces the amount of active inhibitor, but also leads to accumulation of the polymers, causing cell death and organ failure. (wikipedia.org)
Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. (elsevierpure.com)
By applying homology-search and text-mining programs we have found that the Drosophila serine protease inhibitor (serpin) gene sp4 harbours four reactive centre-coding exons. (uni-bielefeld.de)
Fibrotic remodeling genes, such as tissue inhibitor of metalloproteinase (TIMP)-1 and serpin A 3n, were upregulated in males during myocarditis rather than during DCM. (elsevierpure.com)
Identification of serpin determinants of specificity and selectivity for furin inhibition through studies of α1PDX (α1-protease inhibitor Portland)-serpin B8 and furin active-site loop chimeras. (uic.edu)
α1-Protease inhibitor Portland (α1PDX) is an engineered serpin family inhibitor of the proprotein convertase (PC), furin, that exhibits high specificity but limited selectivity for inhibiting furin over other PC family proteases. (uic.edu)
Here, we characterize serpin B8, a natural inhibitor of furin, together with α1PDX-serpin B8 and furin-PC chimeras to identify determinants of serpin specificity and selectivity for furin inhibition. (uic.edu)
previously referred to as antithrombin III) is a 58-kDa molecule belonging to the serine protease inhibitor (serpin) superfamily that plays a central role in anticoagulation and regulating appropriate wound healing in mammalian circulation systems. (medscape.com)
AT belongs to the serpin family of inhibitors, which include heparin cofactor II (HCII), alpha2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), C1-inhibitor, and alpha1-antitrypsin. (medscape.com)
Alpha-1 Antitrypsin (Serpin A1) and secretory leukocyte protease inhibitor (SLPI) have been shown to inhibit ELA2 activity. (novusbio.com)

Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. (wikipedia.org)
That they belonged to a new protein family became apparent on their further alignment with the non-inhibitory egg-white protein ovalbumin, to give what was initially called the alpha1-antitrypsin-antithrombin III-ovalbumin superfamily of serine proteinase inhibitors, but was subsequently succinctly renamed as the Serpins. (wikipedia.org)
The human serpin superfamily consists of at least 35 members that target not only serine proteases, but also selected cysteine proteases and non-protease proteins. (rndsystems.com)
It is a member of the serpin superfamily. (lookformedical.com)
A member of the serpin superfamily found in plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. (lookformedical.com)
Members of serpin superfamily are involved in wide array of cellular processes to control proteolytic activities of eukaryotic organisms. (jgenomics.com)
The members of serpin superfamily have instrumental roles in a variety of physiological and cellular functions and are associated with the vertebrate blood coagulation cascade, complement activation, inflammation, programmed cell death, cell development, and fibrinolysis [ 1 - 3 ]. (jgenomics.com)
These serpin members represent the largest superfamily and most diverse family of protease inhibitors [ 3 ]. (jgenomics.com)

Protease inhibition by serpins controls an array of biological processes, including coagulation and inflammation, and consequently these proteins are the target of medical research. (wikipedia.org)
Although most serpins control proteolytic cascades, some proteins with a serpin structure are not enzyme inhibitors, but instead perform diverse functions such as storage (as in egg white-ovalbumin), transport as in hormone carriage proteins (thyroxine-binding globulin, cortisol-binding globulin) and molecular chaperoning (HSP47). (wikipedia.org)
This active-centre specificity of inhibition was also evident in the many other families of protease inhibitors but the serpins differed from them in being much larger proteins and also in possessing what was soon apparent as an inherent ability to undergo a change in shape. (wikipedia.org)
A member of the serpin family of proteins that is found in plasma and urine. (lookformedical.com)
The serpins (SERine Proteinase INhibitors) are a family of proteins with important physiological roles, including but not limited to the inhibition of chymotrypsin-like serine proteinases. (psu.edu)
Serpins are also an unusual family of proteins in which homologues have native states with different folding topologies. (psu.edu)
Serpins are single domain proteins with an average size: 350-400 amino acids and molecular weights of 40-60 kDa [ 2 - 4 ]. (jgenomics.com)
The research is the first to investigate the folding of proteins know as serpins, implicated in a number of diseases. (umass.edu)
The serpin family of proteins have a highly conserved molecular structure, with 3 beta-sheets and 9 alpha-helices. (medscape.com)

The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases (serine protease inhibitors). (wikipedia.org)
The regulations of proteolytic activity of serine proteases are critical steps to maintain balanced homeostasis and the serine protease inhibitors (serpins) possess capabilities to regulate the proteolytic activities of these serine proteases by inhibitory mechanism [ 1 ]. (jgenomics.com)
An examination revealed the presence of two serpin genes, each coding for two or three likely alternative reactive centre exon cassettes, respectively, also in the Caenorhabditis elegans genome, The occurrence of such serpin genes in some groups of metazoa reflects a parsimonious way to enlarge the adaptive ability of these organisms to cope with a plethora of different serine and cysteine proteases. (uni-bielefeld.de)
[ 14 ] A region known as the reactive center loop (RCL) protrudes above the core of the serpin molecule and has a sequence of amino acids that is complementary to binding sites in the active sites of the target proteases. (medscape.com)
Serine protease inhibitors (SERPINS) regulate activated proteases. (bvsalud.org)
The myxoma virus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated thrombotic, thrombolytic, and complement proteases as a self-defense strategy to combat clearance. (bvsalud.org)

As protease inhibitors, serpins have an array of functions including regulating blood clotting, the complement pathway, extracellular matrix remodeling, and cell motility. (rndsystems.com)
Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known. (lookformedical.com)
Serine proteinase inhibitors (serpins) play a vital regulatory role in a wide range of biological processes, and serpins from viruses have been implicated in pathogen evasion of the host defence system. (elsevierpure.com)
These studies demonstrate that RCL-primed residues, strand 3C exosites, and the furin(298-300) loop are critical determinants of serpin reactivity with furin, which may be exploited in the design of specific and selective α1PDX inhibitors of PCs. (uic.edu)
Sequential changes in gene expression for uPAR and serpins (complement and plasminogen inhibitors) were observed. (bvsalud.org)
Known elastolytic enzyme inhibitors include serine proteinase inhibitors (serpins) and tissue inhibitors of metalloproteinase (TIMPs). (medscape.com)
A mutation unique in serine protease inhibitors (serpins) identified in a family with type II hereditary angioneurotic edema. (lu.se)

Determination of the structures of inhibitory serpins in multiple conformational states permits a detailed analysis of the mechanism of the S → R transition, and of the way in which a single sequence can form two stabilised states of different topology. (psu.edu)
The exon/intron structures and genomic locus comparisons together with sequence phylogenetic analysis, suggested that urochordate serpins are classified into six groups (U1-U6), different from six groups (V1-V6) of vertebrate serpins. (jgenomics.com)
Human α 1 -antitrypsin shared lower sequence identities and similarities with urochordates serpins ranged from 14-29% and 30-49%, respectively. (jgenomics.com)
Based on sequence analyses, all serpins so far described have been classified into one of 16 clades, designated A to P, plus 10 unclassified 'orphan' sequences and this classification system is called as "clade-based classification" system [ 8 ]. (jgenomics.com)
Bm-SPN-2 is one of the largest of the 93 known serpins, due to a 22 amino acid carboxy-terminal extension, and contains the conserved serpin signature sequence. (elsevierpure.com)
Replacing reactive center loop (RCL) sequences of α1PDX with those of serpin B8 demonstrated that both the P4-P1 RXXR recognition sequence as well as the P1'-P5' sequence are critical determinants of serpin specificity for furin. (uic.edu)
The furin(298-300) loop but not the other loops differentially affected furin reactivity with serpin B8 and α1PDX in a manner that depended on the serpin RCL-primed sequence. (uic.edu)
Rapid amplification of the cDNA ends (RACE) and primers designed based on a conserved serpin amino acid motif (NAVYFKG) were used to clone a 1350bp cDNA which encodes a 378 polypeptide with high sequence similarity to several known serpins. (tamu.edu)

Genetic testing of 177 subjects among an Amish community in Berne, Indiana, showed 43 carriers of the SERPIN 1 gene mutation, leading to its inactivation [1]. (longlonglife.org)
The SERPIN 1 gene codes the PAI-1 protein, which is synthesized in fat and liver tissue and helps regulating the dissolution of blood clots in the circulatory system. (longlonglife.org)
The higher the PAI-1 levels are in the body, the more it will show signs of biological aging - and vice-versa, the aging process will be slower in people with low levels of PAI-1, like the Amish with the SERPIN 1 gene [1]. (longlonglife.org)
Vertebrate serpins are extensively studied and reported to be classified into six groups (V1-V6) based on gene structures. (jgenomics.com)
Serpins are thought to have evolved through gene duplication and divergence events, giving rise to a large number of serpin genes within an organism, each encoding a protein with a unique reactive center region and physiological function(s) [ 7 ]. (jgenomics.com)
Thus, serpin A 3n was identified as a gene associated with fibrotic cardiac remodeling and progression to DCM in male myocarditis patients and mice. (elsevierpure.com)
For the first time, we report a functional serpin gene from nematodes that may function in this manner. (elsevierpure.com)
We have named this gene as Haemaphysalis longicornis serpin-1 (HLS1). (tamu.edu)

Serpins bind the protease active site resulting in a major conformational rearrangement that traps the enzyme in a covalent acyl-enzyme intermediate. (rndsystems.com)

Protease inhibitory activity in blood plasma was first reported in the late 1800s, but it was not until the 1950s that the serpins antithrombin and alpha 1-antitrypsin were isolated, with the subsequent recognition of their close family homology in 1979. (wikipedia.org)
The critical role of the active centre residue in determining the specificity of inhibition of serpins was unequivocally confirmed by the finding that a natural mutation of the active centre methionine in alpha1-antitrypsin to an arginine, as in antithrombin, resulted in a severe bleeding disorder. (wikipedia.org)

This together with the subsequent solving of the structure of native (uncleaved) ovalbumin indicated that the inhibitory mechanism of the serpins involved a remarkable conformational shift, with the movement of the exposed peptide loop containing the reactive site and its incorporation as a middle strand in the main beta-pleated sheet that characterises the serpin molecule. (wikipedia.org)

The conformational-change mechanism confers certain advantages, but it also has drawbacks: serpins are vulnerable to mutations that can result in serpinopathies such as protein misfolding and the formation of inactive long-chain polymers. (wikipedia.org)
The nature of this conformational change was revealed with the determination in 1984 of the first crystal structure of a serpin, that of post-cleavage alpha1-antitrypsin. (wikipedia.org)
Subsequent structural studies have revealed an additional advantage of the conformational mechanism in allowing the subtle modulation of inhibitory activity, as notably seen at tissue level with the functionally diverse serpins in human plasma. (wikipedia.org)
Serpins fold to a metastable native state and are susceptible to undergoing spontaneous conformational change to more stable conformers, such as the latent form. (proteopedia.org)
We investigated conformational change in tengpin, an unusual prokaryotic serpin from the extremophile Thermoanaerobacter tengcongensis. (proteopedia.org)

To unravel further the phylogenetic history of serpin genes, we characterized serpin genes from two urochordates ( Ciona intestinalis and Ciona savignyi ). (jgenomics.com)
We found that 39 of 118 (33%) genes identified in acute DCM patients were significantly altered in the heart during CVB3 myocarditis in mice, including serpin A 3n (3.3-fold change, P = 0.0001). (elsevierpure.com)

Y. Wang and H. Ragg, "Angiotensinogen: the multi-faceted nature of an ancient vertebrate serpin", Presented at the 6th International Symposium on the Chemistry and Biology of Serpins, Raleigh, North Carolina, 2011. (uni-bielefeld.de)

Testosterone increased IL-1β levels in the heart (P = 0.02), a cytokine known to regulate cardiovascular remodeling, and IL-1β in turn increased cardiac serpin A 3n mRNA (P = 0.005). (elsevierpure.com)

In addition to the serpin domain, tengpin contains a functionally uncharacterized 56-amino-acid amino-terminal region. (proteopedia.org)

Outside these regions, levels of homology are low, and only a distant relationship can been seen to a Caenorhabditis elegans serpin. (elsevierpure.com)

Moradia com 3 quartos, 2 wc's, 1 sala e cozinha em open space, inserido num lote de terreno com 200m2, numa zona onde impera a Natureza e algumas praias fluviais, a praia de Serpins e a praia da Bogueira, em Casal de Ermio. (century21.pt)

The serpin structures illustrate detailed control of conformation within a single protein. (psu.edu)
Therefore, the function of the N terminus in tengpin resembles protein cofactors that prevent mammalian serpins from spontaneously adopting the latent conformation. (proteopedia.org)

In inhibitory serpins, in the cleaved (R) state the reactive centre loop forms an additional strand within the β-sheet. (psu.edu)

Using gonadectomy and testosterone replacement, we showed that testosterone increased cardiac TIMP-1 (P = 0.04), serpin A 3n (P = 0.007), and matrix metalloproteinase (MMP)-8 (P = 0.04) during myocarditis. (elsevierpure.com)

The initial characterisation of the new family centred on alpha1-antitrypsin, a serpin present in high concentration in blood plasma, the common genetic disorder of which was shown to cause a predisposition to the lung disease emphysema and to liver cirrhosis. (wikipedia.org)

This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. (elsevierpure.com)
We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. (elsevierpure.com)

We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. (elsevierpure.com)
Apart from 36 human serpins, there are more than 3000 serpins, which have now been described from viruses, bacteria, archaea, and other eukaryotes. (jgenomics.com)

Analysis of crystal structures together with mutagenesis studies show that the N terminus of tengpin protects a hydrophobic patch in the serpin domain and functions to trap tengpin in its native metastable state. (proteopedia.org)

It is possible that Bm-SPN-2 could function as a stage-specific serpin in the blood environment of the microfilarial parasite in protection from human immunity and thus may be a good candidate for protective vaccine. (elsevierpure.com)

The term serpin is used to describe these members as well, despite their non-inhibitory function, since they are evolutionarily related. (wikipedia.org)
The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. (elsevierpure.com)

Alignments of PC catalytic domains revealed four variable active-site loops whose role in furin reactivity with serpin B8 was tested by engineering furin-PC loop chimeras. (uic.edu)

Recombinant serpin A 3n treatment induced cardiac fibrosis during CVB3 myocarditis (P = 0.0008) while decreasing MMP-3 (P = 0.04) and MMP-9 (P = 0.03) levels in the heart. (elsevierpure.com)

Modeling of the serpin B8-furin Michaelis complex identified serpin exosites in strand 3C close to the 298-300 loop whose substitution in α1PDX differentially affected furin reactivity depending on the furin loop and serpin RCL-primed sequences. (uic.edu)
The protease-serpin complex is cleared from the circulation by receptor-mediated endocytosis in the liver. (medscape.com)

The N terminus of the serpin, tengpin, functions to trap the metastable native state. (proteopedia.org)

Serpin A3N " has 2 results in Products. (rndsystems.com)
Serpin B6 " has 4 results in Products. (rndsystems.com)

Anatomy1

Organisms3

Chemicals and Drugs32

Analytical, Diagnostic and Therapeutic Techniques and Equipment3

Phenomena and Processes7

Information Science3

Inhibitor10

Superfamily8

Proteins9

Proteases6

Inhibitors7

Sequence8

Gene8

Protease active site1

Antithrombin2

Inhibitory mechanism1

Conformational5

Genes2

Vertebrate1

MRNA1

Amino1

Caenorhabditis1

Casal de Ermio1

Conformation2

Reactive1

Metalloproteinase1

Family1

Molecular2

Viruses2

Structures1

Human1

Describe2

Active site1

Treatment1

Complex2

Functions1

Products2