keyword
https://read.qxmd.com/read/37479104/an-innovative-strategy-to-investigate-microbial-protein-modifications-in-a-reliable-fast-and-sensitive-way-a-therapy-oriented-proof-of-concept-based-on-uv-c-irradiation-of-sars-cov-2-spike-protein
#1
JOURNAL ARTICLE
Sergio Strizzi, Letizia Bernardo, Pasqualina D'Ursi, Chiara Urbinati, Andrea Bianco, Fiona Limanaqi, Andrea Manconi, Maria Milanesi, Alberto Macchi, Dario Di Silvestre, Adalberto Cavalleri, Giovanni Pareschi, Marco Rusnati, Mario Clerici, PierLuigi Mauri, Mara Biasin
The characterization of modifications of microbial proteins is of primary importance to dissect pathogen lifecycle mechanisms and could be useful in identifying therapeutic targets. Attempts to solve this issue yielded only partial and non-exhaustive results. We developed a multidisciplinary approach by coupling in vitro infection assay, mass spectrometry (MS), protein 3D modelling, and surface plasma resonance (SPR). As a proof of concept, the effect of low UV-C (273nm) irradiation on SARS-CoV-2 spike (S) protein was investigated...
July 19, 2023: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/36829940/a-buried-water-network-modulates-the-activity-of-the-escherichia-coli-disulphide-catalyst-dsba
#2
JOURNAL ARTICLE
Geqing Wang, Jilong Qin, Anthony D Verderosa, Lilian Hor, Carlos Santos-Martin, Jason J Paxman, Jennifer L Martin, Makrina Totsika, Begoña Heras
The formation of disulphide bonds is an essential step in the folding of many proteins that enter the secretory pathway; therefore, it is not surprising that eukaryotic and prokaryotic organisms have dedicated enzymatic systems to catalyse this process. In bacteria, one such enzyme is disulphide bond-forming protein A (DsbA), a thioredoxin-like thiol oxidase that catalyses the oxidative folding of proteins required for virulence and fitness. A large body of work on DsbA proteins, particularly Escherichia coli DsbA (EcDsbA), has demonstrated the key role that the Cys30 -XX-Cys33 catalytic motif and its unique redox properties play in the thiol oxidase activity of this enzyme...
February 4, 2023: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/35550505/covalent-binding-of-human-two-domain-cd4-to-an-hiv-1-subtype-c-sosip-664-trimer-modulates-its-structural-dynamics
#3
JOURNAL ARTICLE
Nancy L Tumba, Previn Naicker, Stoyan Stoychev, Mark A Killick, Gavin R Owen, Maria A Papathanasopoulos
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) mediates host cell infection by binding to the cellular receptor CD4. Recombinant Env bound to CD4 has been explored for its potential as an HIV vaccine immunogen as receptor binding exposes otherwise shielded, conserved functional sites. Previous preclinical studies showed an interchain disulphide linkage facilitated between Env and 2dCD4S60C generates an immunogenic complex that elicits potent, broadly neutralizing antibodies (bNAbs) against clinically relevant HIV-1...
July 5, 2022: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/31069776/in-vivo-measurement-of-redox-regulated-tg2-activity
#4
JOURNAL ARTICLE
Arek V Melkonian, Nielson Weng, Brad A Palanski, Chaitan Khosla
Transglutaminase 2 (TG2) is a ubiquitous mammalian enzyme that is implicated in a variety of physiological processes and human diseases. Normally, extracellular TG2 is catalytically dormant due to formation of an allosteric disulphide bond between Cys370 and 371 of the enzyme. In this protocol, we describe a method to reduce this disulphide bond in living mice and to monitor the resulting in vivo TG2 activity. Briefly, exogenous thioredoxin-1 protein (TRX) is prepared and administered as a specific, physiologically relevant reductant of the Cys370-371 disulphide along with the small molecule 5-biotinamidopentylamine (5-BP) as a TG2 activity probe...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/31069768/assays-of-thiol-isomerase-enzymatic-activity
#5
JOURNAL ARTICLE
Roelof H Bekendam, Robert Flaumenhaft
Thiol isomerases are oxidoreductases that mediate disulphide bond formation in nascent proteins of the endoplasmic reticulum to ensure their structural integrity. In addition to its role in protein folding, thiol isomerases can modify allosteric disulphide bonds in both intracellular and extracellular proteins, thereby controlling protein function. The process of disulphide bond formation and cleavage is strictly regulated and responsive to redox conditions. Understanding disulphide bond regulation under different redox environments is critical to understanding physiological and pathological processes related to disulphide bond chemistry...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/31069766/studying-functional-disulphide-bonds-by-computer-simulations
#6
JOURNAL ARTICLE
Frauke Gräter, Wenjin Li
Biochemical and structural data reveal important aspects of the properties and function of a protein disulphide bond. Molecular dynamics simulations can complement this experimental data and can yield valuable insights into the dynamical behavior of the disulphide bond within the protein environment. Due to the increasing accuracy of the underlying energetic description and the increasing computational power at hand, such simulations have now reached a level, at which they can also make quantitative and experimentally testable predictions...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/31069761/classification-of-protein-disulphide-bonds
#7
JOURNAL ARTICLE
Aster E Pijning, Philip Hogg
Protein disulphide bonds are the links between pairs of cysteine residues in the polypeptide chain. These bonds are classified based on the sign of the five dihedral angles that define the cystine residue. Twenty disulphide conformations are possible using this convention and all 20 are represented in protein structures. Force distribution analysis of the pairwise forces between the cysteine residues of the different conformations identified 2 of the 20 as having significant strain: the -RHstaple and -/+RHhook disulphide bonds...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/31003762/allostery-in-coagulation-factor-viia-revealed-by-ensemble-refinement-of-crystallographic-structures
#8
JOURNAL ARTICLE
Anders B Sorensen, Jesper J Madsen, Thomas M Frimurer, Michael T Overgaard, Prafull S Gandhi, Egon Persson, Ole H Olsen
A critical step in injury-induced initiation of blood coagulation is the formation of the complex between the trypsin-like protease coagulation factor VIIa (FVIIa) and its cofactor tissue factor (TF), which converts FVIIa from an intrinsically poor enzyme to an active protease capable of activating zymogens of downstream coagulation proteases. Unlike its constitutively active ancestor trypsin, FVIIa is allosterically activated (by TF). Here, ensemble refinement of crystallographic structures, which uses multiple copies of the entire structure as a means of representing structural flexibility, is applied to explore the impacts of inhibitor binding to trypsin and FVIIa, as well as cofactor binding to FVIIa...
April 2, 2019: Biophysical Journal
https://read.qxmd.com/read/30861549/role-of-cell-surface-lipids-and-thiol-disulphide-exchange-pathways-in-regulating-the-encryption-and-decryption-of-tissue-factor
#9
JOURNAL ARTICLE
Shabbir A Ansari, Usha R Pendurthi, L Vijaya Mohan Rao
Tissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF-FVIIa complex triggers the initiation of the blood coagulation pathway. TF plays an essential role in haemostasis, but an aberrant expression of TF activity contributes to thrombotic disorders. In health, TF pro-coagulant activity on cells is controlled tightly to allow sufficient coagulant activity to achieve haemostasis but not to cause thrombosis. It is achieved largely by selective localization of TF in the body and encryption of TF at the cell surface...
March 12, 2019: Thrombosis and Haemostasis
https://read.qxmd.com/read/30353968/hdx-ms-reveals-orthosteric-and-allosteric-changes-in-apolipoprotein-d-structural-dynamics-upon-binding-of-progesterone
#10
JOURNAL ARTICLE
Claudia S Kielkopf, Madhubrata Ghosh, Ganesh S Anand, Simon H J Brown
Apolipoprotein-D is a glycosylated tetrameric lipocalin that binds and transports small hydrophobic molecules such as progesterone and arachidonic acid. Like other lipocalins, apolipoprotein-D adopts an eight-stranded β-barrel fold stabilised by two intramolecular disulphide bonds, with an adjacent α-helix. Crystallography studies of recombinant apolipoprotein-D demonstrated no major conformational changes upon progesterone binding. Amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) reports structural changes of proteins in solution by monitoring exchange of amide hydrogens in the protein backbone with deuterium...
October 24, 2018: Protein Science
https://read.qxmd.com/read/28027946/how-serpins-transport-hormones-and-regulate-their-release
#11
REVIEW
Robin W Carrell, Randy J Read
The adaptation of the serpin framework and its mechanism to perform diverse functions is epitomised in the hormone carriers of the blood. Thyroxine and the corticosteroids are transported bound in a 1:1 ratio on almost identical sites in the two homologous binding-globulins, TBG and CBG. Recent structural findings show an equilibrated, rather than on-and-off, release of the hormones from the carriers, reflecting small reversible movements of the hinge region of the reactive loop that modify the conformational flexibility of the underlying hormone-binding site...
February 2017: Seminars in Cell & Developmental Biology
https://read.qxmd.com/read/27965358/molecular-mechanisms-of-allosteric-inhibition-of-brain-glycogen-phosphorylase-by-neurotoxic-dithiocarbamate-chemicals
#12
JOURNAL ARTICLE
Cécile Mathieu, Linh-Chi Bui, Emile Petit, Iman Haddad, Onnik Agbulut, Joelle Vinh, Jean-Marie Dupret, Fernando Rodrigues-Lima
Dithiocarbamates (DTCs) are important industrial chemicals used extensively as pesticides and in a variety of therapeutic applications. However, they have also been associated with neurotoxic effects and in particular with the development of Parkinson-like neuropathy. Although different pathways and enzymes (such as ubiquitin ligases or the proteasome) have been identified as potential targets of DTCs in the brain, the molecular mechanisms underlying their neurotoxicity remain poorly understood. There is increasing evidence that alteration of glycogen metabolism in the brain contributes to neurodegenerative processes...
February 3, 2017: Journal of Biological Chemistry
https://read.qxmd.com/read/27766046/posttranslational-forms-of-beta-2-glycoprotein-i-in-the-pathogenesis-of-the-antiphospholipid-syndrome
#13
JOURNAL ARTICLE
Fatima El-Assaad, Steven A Krilis, Bill Giannakopoulos
The antiphospholipid syndrome (APS) is an autoimmune disease characterised by a procoagulant state that predisposes to recurrent thrombosis and miscarriages. Two major discoveries have advanced our understanding of the underlying complex pathogenesis of the APS. The first was the discovery that beta-2 glycoprotein-1 (β2GPI) is the major auto antigen in APS. The second was the discovery in more recent years that β2GPI contains allosteric disulphide bonds susceptible to posttranslational modification that may be involved in the development of autoantibodies in APS...
2016: Thrombosis Journal
https://read.qxmd.com/read/27660393/an-isozyme-specific-redox-switch-in-human-brain-glycogen-phosphorylase-modulates-its-allosteric-activation-by-amp
#14
JOURNAL ARTICLE
Cécile Mathieu, Romain Duval, Angélique Cocaign, Emile Petit, Linh-Chi Bui, Iman Haddad, Joelle Vinh, Catherine Etchebest, Jean-Marie Dupret, Fernando Rodrigues-Lima
Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP)...
November 11, 2016: Journal of Biological Chemistry
https://read.qxmd.com/read/27044983/discovery-and-characterisation-of-a-novel-toxin-from-dendroaspis-angusticeps-named-tx7335-that-activates-the-potassium-channel-kcsa
#15
JOURNAL ARTICLE
Iván O Rivera-Torres, Tony B Jin, Martine Cadene, Brian T Chait, Sébastien F Poget
Due to their central role in essential physiological processes, potassium channels are common targets for animal toxins. These toxins in turn are of great value as tools for studying channel function and as lead compounds for drug development. Here, we used a direct toxin pull-down assay with immobilised KcsA potassium channel to isolate a novel KcsA-binding toxin (called Tx7335) from eastern green mamba snake (Dendroaspis angusticeps) venom. Sequencing of the toxin by Edman degradation and mass spectrometry revealed a 63 amino acid residue peptide with 4 disulphide bonds that belongs to the three-finger toxin family, but with a unique modification of its disulphide-bridge scaffold...
April 5, 2016: Scientific Reports
https://read.qxmd.com/read/26247242/measurement-of-state-specific-association-constants-in-allosteric-sensors-through-molecular-stapling-and-nmr
#16
JOURNAL ARTICLE
Kody J Moleschi, Madoka Akimoto, Giuseppe Melacini
Allostery is a ubiquitous mechanism to control biological function and arises from the coupling of inhibitory and binding equilibria. The extent of coupling reflects the inactive vs active state selectivity of the allosteric effector. Hence, dissecting allosteric determinants requires quantification of state-specific association constants. However, observed association constants are typically population-averages, reporting on overall affinities but not on allosteric coupling. Here we propose a general method to measure state-specific association constants in allosteric sensors based on three key elements, i...
August 26, 2015: Journal of the American Chemical Society
https://read.qxmd.com/read/26075355/amino-terminal-arginylation-targets-endoplasmic-reticulum-chaperone-bip-for-autophagy-through-p62-binding
#17
JOURNAL ARTICLE
Hyunjoo Cha-Molstad, Ki Sa Sung, Joonsung Hwang, Kyoung A Kim, Ji Eun Yu, Young Dong Yoo, Jun Min Jang, Dong Hoon Han, Michael Molstad, Jung Gi Kim, Yoon Jee Lee, Adriana Zakrzewska, Su-Hyeon Kim, Sung Tae Kim, Sun Yong Kim, Hee Gu Lee, Nak Kyun Soung, Jong Seog Ahn, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
We show that ATE1-encoded Arg-transfer RNA transferase (R-transferase) of the N-end rule pathway mediates N-terminal arginylation of multiple endoplasmic reticulum (ER)-residing chaperones, leading to their cytosolic relocalization and turnover. N-terminal arginylation of BiP (also known as GRP78), protein disulphide isomerase and calreticulin is co-induced with autophagy during innate immune responses to cytosolic foreign DNA or proteasomal inhibition, associated with increased ubiquitylation. Arginylated BiP (R-BiP) is induced by and associated with cytosolic misfolded proteins destined for p62 (also known as sequestosome 1, SQSTM1) bodies...
July 2015: Nature Cell Biology
https://read.qxmd.com/read/25700620/inhibition-of-thiol-isomerase-activity-diminishes-endothelial-activation-of-plasminogen-but-not-of-protein-c
#18
JOURNAL ARTICLE
C L Smith, C M Shah, N Kamaludin, M P Gordge
INTRODUCTION: Cell surface thiol isomerase enzymes, principally protein disulphide isomerase (PDI), have emerged as important regulators of platelet function and tissue factor activation via their action on allosteric disulphide bonds. Allosteric disulphides are present in other haemostasis-related proteins, and we have therefore investigated whether thiol isomerase inhibition has any influence on two endothelial activities relevant to haemostatic regulation, namely activation of protein C and activation of plasminogen, with subsequent fibrinolysis...
April 2015: Thrombosis Research
https://read.qxmd.com/read/25635856/photonic-activation-of-plasminogen-induced-by-low-dose-uvb
#19
JOURNAL ARTICLE
Manuel Correia, Torben Snabe, Viruthachalam Thiagarajan, Steffen Bjørn Petersen, Sara R R Campos, António M Baptista, Maria Teresa Neves-Petersen
Activation of plasminogen to its active form plasmin is essential for several key mechanisms, including the dissolution of blood clots. Activation occurs naturally via enzymatic proteolysis. We report that activation can be achieved with 280 nm light. A 2.6 fold increase in proteolytic activity was observed after 10 min illumination of human plasminogen. Irradiance levels used are in the same order of magnitude of the UVB solar irradiance. Activation is correlated with light induced disruption of disulphide bridges upon UVB excitation of the aromatic residues and with the formation of photochemical products, e...
2015: PloS One
https://read.qxmd.com/read/24943126/relative-motions-between-left-flipper-and-dorsal-fin-domains-favour-p2x4-receptor-activation
#20
JOURNAL ARTICLE
Wen-Shan Zhao, Jin Wang, Xiao-Juan Ma, Yang Yang, Yan Liu, Li-Dong Huang, Ying-Zhe Fan, Xiao-Yang Cheng, Hong-Zhuan Chen, Rui Wang, Ye Yu
Channel gating in response to extracellular ATP is a fundamental process for the physiological functions of P2X receptors. Here we identify coordinated allosteric changes in the left flipper (LF) and dorsal fin (DF) domains that couple ATP-binding to channel gating. Engineered disulphide crosslinking or zinc bridges between the LF and DF domains that constrain their relative motions significantly influence channel gating of P2X4 receptors, confirming the essential role of these allosteric changes. ATP-binding-induced alterations in interdomain hydrophobic interactions among I208, L217, V291 and the aliphatic chain of K193 correlate well with these coordinated relative movements...
2014: Nature Communications
keyword
keyword
52474
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.