Low-molecular-weight (LMW) thiols are involved in many processes in all organisms, playing a protective role against reactive species, heavy metals, toxins and antibiotics. Actinobacteria, such as Mycobacterium tuberculosis, use the LMW thiol mycothiol (MSH) to buffer the intracellular redox environment. The NADPH-dependent FAD-containing oxidoreductase mycothiol disulfide reductase (Mtr) is known to reduce oxidized mycothiol disulfide (MSSM) to MSH, which is crucial to maintain the cellular redox balance. In this work, the first crystal structures of Mtr are presented, expanding the structural knowledge and understanding of LMW thiol reductases. The structural analyses and docking calculations provide insight into the nature of Mtrs, with regard to the binding and reduction of the MSSM substrate, in the context of related oxidoreductases. The putative binding site for MSSM suggests a similar binding to that described for the homologous glutathione reductase and its respective substrate glutathione disulfide, but with distinct structural differences shaped to fit the bulkier MSSM substrate, assigning Mtrs as uniquely functioning reductases. As MSH has been acknowledged as an attractive antitubercular target, the structural findings presented in this work may contribute towards future antituberculosis drug development.

Lanthanide ions have ideal chemical properties for catalysis, such as hard Lewis acidity, fast ligand-exchange kinetics, high coordination-number preferences and low geometric requirements for coordination. As a result, many small-molecule lanthanide catalysts have been described in the literature. Yet, despite the ability of enzymes to catalyse highly stereoselective reactions under gentle conditions, very few lanthanoenzymes have been investigated. In this work, the mononuclear binding of europium(III) and gadolinium(III) to the active site of a mutant of the model enzyme phosphotriesterase are described using X-ray crystallography at 1.78 and 1.61 Å resolution, respectively. It is also shown that despite coordinating a single non-natural metal cation, the PTE-R18 mutant is still able to maintain esterase activity.

Human peptidylarginine deiminase isoform VI (PAD6), which is predominantly limited to cytoplasmic lattices in the mammalian oocytes in ovarian tissue, is essential for female fertility. It belongs to the peptidylarginine deiminase (PAD) enzyme family that catalyzes the conversion of arginine residues to citrulline in proteins. In contrast to other members of the family, recombinant PAD6 was previously found to be catalytically inactive. We sought to provide structural insight into the human homologue to shed light on this observation. We report here the first crystal structure of PAD6, determined at 1.7 Å resolution. PAD6 follows the same domain organization as other structurally known PAD isoenzymes. Further structural analysis and size-exclusion chromatography show that PAD6 behaves as a homodimer similar to PAD4. Differential scanning fluorimetry suggests that PAD6 does not coordinate Ca2+ which agrees with acidic residues found to coordinate Ca2+ in other PAD homologs not being conserved in PAD6. The crystal structure of PAD6 shows similarities with the inactive state of apo PAD2, in which the active site conformation is unsuitable for catalytic citrullination. The putative active site of PAD6 adopts a non-productive conformation that would not allow protein–substrate binding due to steric hindrance with rigid secondary structure elements. This observation is further supported by the lack of activity on the histone H3 and cytokeratin 5 substrates. These findings suggest a different mechanism for enzymatic activation compared with other PADs; alternatively, PAD6 may exert a non-enzymatic function in the cytoplasmic lattice of oocytes and early embryos.

The complex [Pt(C9H6NO)Cl(C2H4)], (I), was synthesized and structurally characterized by ESI mass spectrometry, IR, NMR spectroscopy, DFT calculations and X-ray diffraction. The results showed that the deprotonated 8-hy­droxy­quinoline (C9H6NO) coordinates with the PtII atom via the N and O atoms while the ethyl­ene coordinates in the η2 manner and in the trans position compared to the coordinating N atom. The crystal packing is characterized by C—H⋯O, C—H⋯π, Cl⋯π and Pt⋯π inter­actions. Complex (I) showed high selective activity against Lu-1 and Hep-G2 cell lines with IC50 values of 0.8 and 0.4 µM, respectively, 54 and 33-fold more active than cisplatin. In particular, complex (I) is about 10 times less toxic to normal cells (HEK-293) than cancer cells Lu-1 and Hep-G2. Furthermore, the reaction of complex (I) with guanine at the N7 position was proposed and investigated using the DFT method. The results indicated that replacement of the ethyl­ene ligand with guanine is thermodynamically more favorable than the Cl ligand and that the reaction occurs via two consecutive steps, namely the replacement of ethyl­ene with H2O and the water with the guanine mol­ecule.

Over the past century, technological advancements have vastly improved volcano monitoring. One key innovation was the introduction of modern borehole tiltmeters, devices that measure very small changes in the inclination of the volcano’s surface.  

To meet the bodys daily energy and nutritional needs while minimizing risk for chronic disease, adults should get 45 percent to 65 percent of their calories from carbohydrates, 20 percent to 35 percent from fat, and 10 percent to 35 percent from protein.

A new report from the National Academies of Sciences, Engineering, and Medicine – which reviews a separate report by a federally funded laboratory that examines options for treating low-activity radioactive waste at the Hanford Nuclear Reservation -- is available for public comment until Oct. 31.

The I-SOON data leak confirms that this contractor is involved in cyberespionage for China, while Iran-aligned groups step up aggressive tactics following the Hamas-led attack on Israel in 2023

An overview of the activities of selected APT groups investigated and analyzed by ESET Research in Q2 2024 and Q3 2024

The study found that carbohydrates and polyphenols in prunes act as prebiotics and help restore bone health.

 
Next-generation IoT system digitizes daily processes, adds capabilities, streamlines logistics and provides actionable, on-demand machine insights.

Two studies demonstrate that older adults may be able to live longer, healthier lives by increasing physical activity that doesn’t have to be strenuous to be effective, according to preliminary research presented at the American Heart Association’s Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2020. The EPI Scientific Sessions, March 3-6 in Phoenix, is a premier global exchange of the latest advances in population-based cardiovascular science for researchers and clinicians.

In the consumer packaged goods space there’s no shortage of celebrity-backed products, particularly beverages. Although proliferating across all segments, alcohol brands are seeing the most activity.

Taxpayers in certain niches more likely to be audited in 2024 according to Vancouver Chartered Accountants at Mew and Company.

Southern California's Premier FBO to Exhibit at NBAA–BACE 2023

Intuitive complementary sports betting app empowers sports bettors with insights across major sports books and betting platforms

Do you want to get a free high-quality human hair wig? Nadula Hair is launching an interesting new fashion launched activity and tape it my way challenge activity on May 22th.

The tumor microenvironment (TME) is a major obstacle that limits effective cancer treatments. Various cells around the tumor promote immunosuppression and

What processes provide energy to the solar wind as it travels away from the Sun and throughout the solar system? This is what a recent study published in S

What did Mars look like billions of years ago? This is what a recent study presented at the Europlanet Science Congress (EPSC) 2024 hopes to address as a t

What processes provide energy to the solar wind as it travels away from the Sun and throughout the solar system? This is what a recent study published in S

What did Mars look like billions of years ago? This is what a recent study presented at the Europlanet Science Congress (EPSC) 2024 hopes to address as a t

The tumor microenvironment (TME) is a major obstacle that limits effective cancer treatments. Various cells around the tumor promote immunosuppression and

What did Mars look like billions of years ago? This is what a recent study presented at the Europlanet Science Congress (EPSC) 2024 hopes to address as a t

استمرت المواجهة في السودان بين القوات المسلحة السودانية وقوات الدعم السريع لعدة أشهر قبل أن تتصاعد إلى نزاع مسلح في 15 أبريل 2023. بالإضافة ة إلى جانب الكارثة الإنسانية، عطل النزاع العديد من الخدمات العامة مثل الكهرباء والمياه والخدمات الصحية والخدمات المصرفية، بينما تعطل أيضا الوصول إلى الأسواق، مما أدى إلى ندرة كبيرة في السلع والخدمات. وقد دمر الصراع البنية التحتية الرئيسية، وقيد التجارة المحلية والدولية وعطل أنشطة الإنتاج وسلاسل الموردين.

دخل النزاع المسلح بين القوات المسلحة السودانية وقوات الدعم السريع في السودان شهره السادس منذ اندلاعه في 15 أبريل 2023، دون أي مؤشرات على انتهائه قريبا. تسببت الحرب في كارثة إنسانية حادة، دمرت البنية التحتية الرئيسية، وقيدت أنشطة التجارة والإنتاج. علاوة على ذلك، أدى ذلك إلى تعطيل الوصول إلى المرافق العامة والخدمات المالية والأسواق، مما أدى إلى ندرة كبيرة في السلع والخدمات. في هذه الورقة، نستخدم إطار نمذجة مضاعف مصفوفة المحاسبة الاجتماعية لتقييم الآثار الاقتصادية على مستوى الاقتصاد لهذه الاضطرابات في النشاط الاقتصادي والموارد الإنتاجية وسبل العيش.

New Work Activity - Extended Partial Alley Closure at t he Alley east of 4801 thru 4838 N. Broadway.

New Work Activity- Extended West Bound Lane Closure at W. Bryn Mawr Avenue between N. Broadway and N. Winthrop Avenue for Street, Sewer Reconstruction & Station Utility Connection

There will be intermittent street closures on W Ardmore at the CTA tracks to allow crews to hoist construction materials to track level.

New Work Activity Extended Partial-Alley Closure at the alley east of 4801 thru 4838 N. Broadway for Lawrence Station Construction.

Toronto, ON — The University of Toronto’s Faculty of Kinesiology and Physical Education has launched the Mental Health and Physical Activity Research Centre (MPARC) — one of the first research facilities to integrate the study of physical activity and mental health in Canada and internationally. Opened on February 25, this multidisciplinary centre will address the […]

Since April, Recruiter.com has been tracking recruiter sentiment and hiring activity through the Recruiter Index®, an ongoing survey of recruiters and hiring professionals on the front lines of the job market today. While May's poll showed significant improvements in recruiter confidence and job market activity over April's, June's results are strikingly positive. For the first time since the survey began, the majority of recruiters — 51.4 percent — believe their job requirement ...

Kobe JALT (Kobe Chapter of the Japan Association for Language Teaching). December 8 (Sun), 14:00-15:30 in Kobe, Hyogo. Stephen McNamara (Kwansei Gakuin University).

Conformance of ITU-T H.810 personal health system: Personal Health Devices interface Part 5H: Independent living activity hub

Conformance of ITU-T H.810 personal health system: Personal Health Devices interface Part 5F: Cardiovascular fitness and activity monitor

GSTP-GSAD - Generic Sound Activity Detector

Merger and acquisition (M&A) activity in the pharmaceutical contract manufacturing industry declined in 2023 compared to 2021-22. High inflation and interest rates along with an uncertain business environment disincentivized investment.

Neuroscientists introduce a new tool to detect hippocampal activity.

A simple framework for hosting bots on the Fediverse

“The Bermuda Police Service [BPS] conducted proactive patrols island wide and responded to various calls for service, during the Remembrance Day holiday weekend,” the police said. A police spokesperson said, “However, there were no major incidents of anti-social behaviour reported. Of note, from 5pm Friday, 8th November until 5am Tuesday, 12th November 2024, a total of […]

Bermuda Hospitals Board [BHB] is is reminding the public that the risk of stroke can be reduced with physical activity. A spokesperson said, “Bermuda Hospitals Board’s Emergency Department sees an average of five people every week who are experiencing a stroke. That’s over 200 people every year.” Dr Srinath Meadipudi, BHB Primary Stroke Centre Director, […]

Japanese encephalitis virus activity in the Kimberley  Government of Western Australia Department of Health

National survey highlights vibrancy and growth of campus research

The Princeton professor's research follows elephants, wolves and urban lizards. He hosts the new PBS series, "Human Footprint."

Over Sukkot, over 150 young Russian-speaking immigrants gathered to celebrate the opening of the center, SSY stated. 

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

Mary G. McCoy
Jun 1, 2002; 43:921-929
Research Articles

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.