A novel conserved B-cell epitope in pB602L of African swine fever virus.

African swine fever virus (ASFV) is a complex DNA virus and the only member of the Asfarviridae family. It causes high mortality and severe economic losses in pigs. The ASFV pB602L protein plays a key role in virus assembly and functions as a molecular chaperone of the major capsid protein p72.

Structural and Functional Insights into the Stealth Protein CpsY of .

() is an important and harmful intracellular pathogen that is responsible for the cause of tuberculosis (TB). capsular polysaccharides can misdirect the host's immune response pathways, resulting in additional challenges in TB treatment. These capsule polysaccharides are biosynthesized by stealth proteins, including CpsY.

Recombinant expression and functional characterization of FadD2 protein in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) is a crucial and highly destructive intracellular pathogen responsible for causing tuberculosis (TB). The emergence and dissemination of multi-drug resistant Mtb has further aggravated the TB crisis, leading to high mortality. Mtb FadD2 is a fatty acyl-coenzyme A (CoA) synthetase that modifies the cell envelope and plays an important role in reducing Mtb susceptibility to pyrazinoic acid (POA).

Suramin Disturbs the Association of the N-Terminal Domain of SARS-CoV-2 Nucleocapsid Protein with RNA.

Suramin was originally used as an antiparasitic drug in clinics. Here, we demonstrate that suramin can bind to the N-terminal domain of SARS-CoV-2 nucleocapsid protein (N-NTD) and disturb its interaction with RNA. The BLI experiments showed that N-NTD interacts suramin with a dissociate constant (K = 2.

Cefotetan-bound human RKIP involves in Ras/Raf1/MEK/ERK signaling pathway.

Cefotetan is widely used to treat bacterial infections in the clinic owing to its broad spectrum of antibacterial activity. In the present study, we demonstrate that cefotetan can bind to the conserved ligand-binding pocket of human Raf1 kinase inhibitory protein (hRKIP), which acts as a negative regulator of the Ras/Raf1/MEK/ERK signaling pathway. The cefotetan-bound hRKIP adopts a rigid structure with insufficient space for binding Raf1 kinase, thereby reliving the inhibitory activity of hRKIP in the Ras/Raf1/MEK/ERK signaling pathway and enhancing the phosphorylation level of ERK.

Crystal structure of the polyketide cyclase from .

About 40% of proteins are classified as conserved hypothetical proteins in (TB). Identification and characterization of these proteins are beneficial to understand the pathogenesis of TB and exploiting novel drugs for TB treatments. The polyketide cyclase, a protein from ( PC) has been annotated as a hypothetical protein in Uniprot database.

Discovery and Structural and Functional Characterization of a Novel A-Superfamily Conotoxin Targeting α9α10 Nicotinic Acetylcholine Receptor.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels widely distributed in the central peripheral nervous system and muscles which participate in rapid synaptic transmission. The α9α10 nAChR is an acetylcholine receptor subtype and is involved in chronic pain. In the present study, a new A-superfamily conotoxin Bt14.

ADP-Induced Conformational Transition of Human Adenylate Kinase 1 Is Triggered by Suppressing Internal Motion of αα and αα Fragments on the ps-ns Timescale.

Human adenylate kinase 1 (AK1) plays a vital role in the energetic and metabolic regulation of cell life, and impaired functions of AK1 are closely associated with many diseases. In the presence of Mg ions, AK1 in vivo can catalyze two ADP molecules into one ATP and one AMP molecule, activating the downstream AMP signaling. The ADP-binding also initiates AK1 transition from an open conformation to a closed conformation.

H, C, N backbone and side-chain chemical shift assignments of the polyketide cyclase from Mycobacterium tuberculosis.

Polyketide cyclase from Mycobacterium tuberculosis (MtPC) is related to the formation of sterol derivatives, which may play a role in immune escape in the initial stage of macrophage infection by Mycobacterium tuberculosis. However, the structure and specific functions of MtPC are still unknown. Here we report the backbone and side-chain NMR resonance assignments for the MtPC.

H, C, N backbone and side-chain NMR assignments of the C-terminal domain of Mycobacterium Tuberculosis ribosome maturation factor RimM.

Tuberculosis (TB), a lethal disease caused by Mycobacterium tuberculosis (Mtb) infection, develops multidrug-resistance and needs new drugs for effective treatment. As a ribosome maturation factor protein, RimM plays an essential role in the bacterial ribosome assembly and is a potential target for antibiotics against TB. RimM is involved in the incorporation of ribosomal protein S19 into the 30 S ribosomal subunit, where the C-terminal domain of RimM is speculated to bind S19.

α-Conotoxin Bt1.8 from Conus betulinus selectively inhibits α6/α3β2β3 and α3β2 nicotinic acetylcholine receptor subtypes.

α-Conotoxins are small disulfide-rich peptides found in the venom of marine cone snails and are potent antagonists of nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential therapeutic applications for the treatment of chronic pain or neurological diseases and disorders. In the present study, we synthesized and functionally characterized a novel α-conotoxin Bt1.

Structural Basis for the C-Terminal Domain of Ribosome Maturation Factor RimM to Bind Ribosomal Protein S19.

Multidrug-resistant tuberculosis (TB) is a serious threat to public health, calling for the development of new anti-TB drugs. Chaperon protein RimM, involved in the assembly of ribosomal protein S19 into 30S ribosomal subunit during ribosome maturation, is a potential drug target for TB treatment. The C-terminal domain (CTD) of RimM is primarily responsible for binding S19.

H, C, N backbone and side-chain resonance assignments of the pathogenic G131V mutant of human prion protein (91-231).

Human prion disease, also known as transmissible spongiform encephalopathy (TSEs), is caused by the conformational conversion of the normal cellular prion protein (PrP) into the scrapie form (PrP). Pathogenic point mutations of prion proteins typically facilitate conformational conversion and lead to inherited prion diseases. A previous study has demonstrated that the pathogenic G131V mutation of human prion protein (HuPrP) brings in Gerstmann-Sträussler-Scheinker syndrome.

Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein.

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway.

Discovery and evaluation of new compounds targeting ribosomal protein S1 in antibiotic-resistant Mycobacterium Tuberculosis.

The emergence of antibiotic-resistant Mycobacterium Tuberculosis (Mtb) infections compels new treatment strategies, of which targeting trans-translation is promising. During the trans-translation process, the ribosomal protein S1 (RpsA) plays a key role, and the Ala438 mutant is related to pyrazinamide (PZA) resistance, which shows its effects after being hydrolysed to pyrazinoic acid (POA). In this study, based on the structure of the RpsA C-terminal domain (RpsA-CTD) and POA complex, new compounds were designed.

Biophysical characterization of oligomerization and fibrillization of the G131V pathogenic mutant of human prion protein.

The pathogenesis of fatal neurodegenerative prion diseases is closely associated with the conversion of α-helix-rich cellular prion protein into β-sheet-rich scrapie form. Pathogenic point mutations of prion proteins usually promote the conformational conversion and trigger inherited prion diseases. The G131V mutation of human prion protein (HuPrP) was identified to be involved in Gerstmann-Sträussler-Scheinker syndrome.

Recombinant expression, biophysical and functional characterization of ClpS from Mycobacterium tuberculosis.

Intracellular proteolysis is attracting more and more attention for its unique and important character in Mycobacterium tuberculosis (Mt). The ClpS protein from Mt (MtClpS) plays a critical role in intracellular proteolysis by recognizing N-end rule substrates, which makes it become a potential target for antibacterial drugs. However, the molecular mechanism of MtClpS recognizing N-end rule substrates remains unclear.

Biophysical and functional characterizations of recombinant RimI acetyltransferase from Mycobacterium tuberculosis.

Nα-acetylation is a universal protein modification related to a wide range of physiological processes in eukaryotes and prokaryotes. RimI, an Nα-acetyltransferase in Mycobacterium tuberculosis, is responsible for the acetylation of the α-amino group of the N-terminal residue in the ribosomal protein S18. Despite growing evidence that protein acetylation may be correlated with the pathogenesis of tuberculosis, no structural information is yet available for mechanistically understanding the MtRimI acetylation.

Crystal structure of the N domain of Lon protease from Mycobacterium avium complex.

Lon protease is evolutionarily conserved in prokaryotes and eukaryotic organelles. The primary function of Lon is to selectively degrade abnormal and certain regulatory proteins to maintain the homeostasis in vivo. Lon mainly consists of three functional domains and the N-terminal domain is required for the substrate selection and recognition.

Structural basis for the complete resistance of the human prion protein mutant G127V to prion disease.

Prion diseases are caused by the propagation of misfolded cellular prion proteins (PrPs). A completely prion disease-resistant genotype, V127M129, has been identified in Papua New Guinea and verified in transgenic mice. To disclose the structural basis of the disease-resistant effect of the G127V mutant, we determined and compared the structural and dynamic features of the G127V-mutated human PrP (residues 91-231) and the wild-type PrP in solution.

Anti-leprosy drug Clofazimine binds to human Raf1 kinase inhibitory protein and enhances ERK phosphorylation.

Human Raf1 kinase inhibitory protein (hRKIP) is an important modulator of the Ras/Raf1/MEK/ERK signaling pathway. Here, we demonstrated that anti-leprosy drug Clofazimine can bind to hRKIP with a significantly stronger affinity than the endogenous substrate phosphatidylethanolamine (PE) by using Biolayer interference technology. Moreover, we identified that residues P74, S75, K80, P111, P112, V177, and P178 play crucial roles in the binding of hRKIP to Clofazimine by using a combination of Nuclear Magnetic Resonance spectroscopy and molecular docking approach.

Structural basis for ribosome protein S1 interaction with RNA in trans-translation of Mycobacterium tuberculosis.

Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown.

Distinct effects of mutations on biophysical properties of human prion protein monomers and oligomers.

Prion diseases are a group of fatal neurodegenerative illnesses, resulting from the conformational conversion of the cellular prion protein (PrP) into a misfolded form (PrP). The formation of neurotoxic soluble prion protein oligomer (PrP) is regarded as a key step in the development of prion diseases. About 10%-15% of human prion diseases are caused by mutations in the prion protein gene; however, the underlying molecular mechanisms remain unclear.

Unique Properties of the Rabbit Prion Protein Oligomer.

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders infecting both humans and animals. Recent works have demonstrated that the soluble prion protein oligomer (PrPO), the intermediate of the conformational transformation from the host-derived cellular form (PrPC) to the disease-associated Scrapie form (PrPSc), exerts the major neurotoxicity in vitro and in vivo. Rabbits show strong resistance to TSEs, the underlying mechanism is unclear to date.

Expression, purification and characterization of Esx-1 secretion-associated protein EspL from Mycobacterium tuberculosis.

The Esx-1 cluster encodes a special secretion system that is important for granuloma formation and virulence when Mycobacterium tuberculosis infects the host. As one of the 'core' genes in the cluster, Rv3880c gene codes an Esx-1 secretion-associated protein EspL from Mycobacterium tuberculosis (MtEspL). It has been reported that EspL had a strong influence on the secretion of other two virulence factors, EsxA and EspE.