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About 24,280 results

A dimer between monomers and hexamers-Oligomeric variations in glucosamine-6-phosphate ...
https://doi.org/10.1371/journal.pone.0271654
PloS One; Srinivasachari S, Tiwari VR et. al.

Jan 5th, 2023 - In bacteria that live in hosts whose terminal sugar is a sialic acid, Glucosamine-6-phosphate deaminase (NagB) catalyzes the last step in converting sialic acid into Fructose-6-phosphate. These bacteria then use the Fructose-6-phosphate as an energy source. The enzyme NagB exists as a hexamer in Gram-negative bacteria and is allosterically regulated. In Gram-positive bacteria, it exists as a mo...

Flavivirus proteases: The viral Achilles heel to prevent future pandemics.
https://doi.org/10.1016/j.antiviral.2022.105516
Antiviral Research; Teramoto T, Choi KH et. al.

Jan 1st, 2023 - Flaviviruses are important human pathogens and include dengue (DENV), West Nile (WNV), Yellow fever virus (YFV), Japanese encephalitis (JEV) and Zika virus (ZIKV). DENV, transmitted by mosquitoes, causes diseases ranging in severity from mild dengue fever with non-specific flu-like symptoms to fatal dengue hemorrhagic fever and dengue shock syndrome. DENV infections are caused by four serotypes...

Role of the Bruton tyrosine kinase pathway in multiple sclerosis.
https://doi.org/10.37765/ajmc.2022.89312
The American Journal of Managed Care; Nair KV

Dec 23rd, 2022 - Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative condition that results in progressive accumulation of disability over the course of the disease. MS presents heterogeneously, and, as the disease progresses, patients develop a range of physical and neurologic problems that include reduced mobility, cognitive impairment, weakness, fatigue, pain, and defects in speech or vi...

Mycobacterial MenG: Partial Purification, Characterization, and Inhibition.
https://doi.org/10.1021/acsinfecdis.2c00190
ACS Infectious Diseases; Pujari V, Rozman K et. al.

Nov 24th, 2022 - Menaquinone (MK) is an essential component of the electron transport chain (ETC) in the gram-variable Mycobacterium tuberculosis and many Gram-positive pathogens. Three genes in the M. tuberculosis genome were annotated as methyltransferases involved in lipoquinone synthesis in mycobacteria. Heterologous expression of Rv0558 complemented an ubiE (the quinone C-methyltransferase involved in ubiq...

Dephospho-Coenzyme A Kinase Is an Exploitable Drug Target against Plasmodium falciparum...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9664868
Antimicrobial Agents and Chemotherapy; Nurkanto A, Imamura R et. al.

Nov 1st, 2022 - Malaria is a mosquito-borne fatal infectious disease that affects humans and is caused by Plasmodium parasites, primarily Plasmodium falciparum. Widespread drug resistance compels us to discover novel compounds and alternative drug discovery targets. The coenzyme A (CoA) biosynthesis pathway is essential for the malaria parasite P. falciparum. The last enzyme in CoA biosynthesis, dephospho-CoA ...

Relationship between Salivary Amylase and Xerostomia in Intensity-Modulated Radiation T...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9497840
Current Oncology (Toronto, Ont.); De Felice F, Scarabelli MG et. al.

Sep 23rd, 2022 - A single-institution prospective pilot study was conducted to the assess correlation between salivary amylase and xerostomia in patients with head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT). Serum saliva amylase, clinician-reported xerostomia (using Common Terminology Criteria for Adverse Events), and patient-reported xerostomia (using 8-item s...

SIRT1 inactivation switches reactive astrocytes to an antiinflammatory phenotype in CNS...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663155
The Journal of Clinical Investigation; Zhang W, Xiao D et. al.

Sep 23rd, 2022 - Astrocytes are highly heterogeneous in their phenotype and function, which contributes to CNS disease, repair, and aging; however, the molecular mechanism of their functional states remains largely unknown. Here, we show that activation of sirtuin 1 (SIRT1), a protein deacetylase, played an important role in the detrimental actions of reactive astrocytes, whereas its inactivation conferred thes...

Lysosomal cathepsin D mediates endogenous mucin glycodomain catabolism in mammals.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522329
Proceedings of the National Academy of Sciences of the Un... Pedram K, Laqtom NN et. al.

Sep 20th, 2022 - Mucins are functionally implicated in a range of human pathologies, including cystic fibrosis, influenza, bacterial endocarditis, gut dysbiosis, and cancer. These observations have motivated the study of mucin biosynthesis as well as the development of strategies for inhibition of mucin glycosylation. Mammalian pathways for mucin catabolism, however, have remained underexplored. The canonical v...

Enterovirus 3C Protease Cleaves TRIM7 To Dampen Its Antiviral Activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555159
Journal of Virology; Fan W, McDougal MB et. al.

Sep 16th, 2022 - Mammalian TRIM7 is an antiviral protein that inhibits multiple human enteroviruses by degrading the viral 2BC protein. Whether TRIM7 is reciprocally targeted by enteroviruses is not known. Here, we report that the 3C protease (3Cpro) from two enteroviruses, coxsackievirus B3 (CVB3) and poliovirus, targets TRIM7 for cleavage. CVB3 3Cpro cleaves TRIM7 at glutamine 24 (Q24), resulting in a truncat...

A kinase-independent function of cyclin-dependent kinase 6 promotes outer radial glia e...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499540
Proceedings of the National Academy of Sciences of the Un... Wang L, Park JY et. al.

Sep 13th, 2022 - The neocortex, the center for higher brain function, first emerged in mammals and has become massively expanded and folded in humans, constituting almost half the volume of the human brain. Primary microcephaly, a developmental disorder in which the brain is smaller than normal at birth, results mainly from there being fewer neurons in the neocortex because of defects in neural progenitor cells...

Adaptive Mutation in the Main Protease Cleavage Site of Feline Coronavirus Renders the ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472640
Journal of Virology; Jiao Z, Yan Y et. al.

Aug 25th, 2022 - The rapid global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused serious health problems, highlighting the urgent need for antiviral drugs. The viral main protease (Mpro) plays an important role in viral replication and thus remains the target of choice for the prevention or treatment of several viral diseases due to high sequence and structural conservation...

Bacterial Hydratases Involved in Steroid Side Chain Degradation Have Distinct Substrate...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491828
Journal of Bacteriology; Schroeter KL, Abraham N et. al.

Aug 25th, 2022 - Actinobacterial MaoC family enoyl coenzyme A (CoA) hydratases catalyze the addition of water across the double bond of CoA esters during steroid side chain catabolism. We determined that heteromeric MaoC type hydratases, exemplified by ChsH1-ChsH2Mtb of Mycobacterium tuberculosis and CasM-CasORjost from Rhodococcus jostii RHA1, are specific toward a 3-carbon side chain steroid metabolite, consi...

A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436381
Proceedings of the National Academy of Sciences of the Un... Guillén-Samander A, Wu Y et. al.

Aug 23rd, 2022 - Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell su...

Colistin-degrading proteases confer collective resistance to microbial communities duri...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389796
Microbiome Lee DH, Cha JH et. al.

Aug 19th, 2022 - The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections. A bacterial strain of the Gram-negative opportunistic pathogen Stenotrop...

The mechanism of RNA capping by SARS-CoV-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492545
Nature Park GJ, Osinski A et. al.

Aug 10th, 2022 - The RNA genome of SARS-CoV-2 contains a 5' cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response1-4. How this cap is made in SARS-CoV-2 is not completely understood. Here we reconstitute the N7- and 2'-O-methylated SARS-CoV-2 RNA cap (7MeGpppA2'-O-Me) using virally encoded non-structural proteins (nsps). We show that the kin...

Structures of the mannose-6-phosphate pathway enzyme, GlcNAc-1-phosphotransferase.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388126
Proceedings of the National Academy of Sciences of the Un... Gorelik A, Illes K et. al.

Aug 9th, 2022 - The mannose-6-phosphate (M6P) pathway is responsible for the transport of hydrolytic enzymes to lysosomes. N-acetylglucosamine-1-phosphotransferase (GNPT) catalyzes the first step of tagging these hydrolases with M6P, which when recognized by receptors in the Golgi diverts them to lysosomes. Genetic defects in the GNPT subunits, GNPTAB and GNPTG, cause the lysosomal storage diseases mucolipidos...

Coronaviruses exploit a host cysteine-aspartic protease for replication.
https://doi.org/10.1038/s41586-022-05148-4
Nature Chu H, Hou Y et. al.

Aug 4th, 2022 - Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link ...

Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic ki...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335328
Proceedings of the National Academy of Sciences of the Un... Akbari M, West JD et. al.

Jul 23rd, 2022 - Autosomal dominant polycystic kidney disease (ADPKD) affects more than 500,000 individuals in the United States alone. In most cases, ADPKD is caused by a loss-of-function mutation in the PKD1 gene, which encodes polycystin-1 (PC1). Previous studies reported that PC1 interacts with atypical protein kinase C (aPKC). Here we show that PC1 binds to the ζ isoform of aPKC (PKCζ) and identify two PKC...

Tropism of SARS-CoV-2 for human cortical astrocytes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335272
Proceedings of the National Academy of Sciences of the Un... Andrews MG, Mukhtar T et. al.

Jul 21st, 2022 - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function of vital organ systems, with particularly severe impact on respiratory function. Neurological symptoms, which range in severity, accompany as many as one-third of COVID-19 cases, indicating a potential vulnerability of neural cell types. To assess whether human cortica...

A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebr...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304032
Proceedings of the National Academy of Sciences of the Un... Deen MC, Zhu Y et. al.

Jul 21st, 2022 - Loss of activity of the lysosomal glycosidase β-glucocerebrosidase (GCase) causes the lysosomal storage disease Gaucher disease (GD) and has emerged as the greatest genetic risk factor for the development of both Parkinson disease (PD) and dementia with Lewy bodies. There is significant interest into how GCase dysfunction contributes to these diseases, however, progress toward a full understand...