It's alive! Watch Benedict Cumberbatch and Jonny Lee Miller switch off in the lead roles in a stage adaptation of "Frankenstein."

Hold on to your wig! RuPaul's annual DragCon is going online. Here's how you can stream it for free.

The experimental theater company revisits Shakespeare using a 1964 filmed performance of Richard Burton. Here's how to stream it for free.

London Fire Brigade Museum secures National Lottery support

The author of "Sweetbitter" juggles child care and promoting her new L.A. area memoir, "Stray," reads poetry and takes solace in "The Office."

Dodge offers two outrageous muscle cars — Hellcat iterations of its Charger and Challenger — that capture the magic of the 1960s horsepower wars.

They may not be classics, but people are watching and talking about 'Trolls World Tour,' 'The Platform' and 'Onward.'

Something sketchy this way comes: "30 Rock" alum Jack McBrayer hosts "The Second City Presents: The Last Show Left on Earth."

See Susan Egan ("Beauty and the Beast"), Krysta Rodriguez ("Hercules") and Christian Borle ("Mary Poppins") in a benefit for a COVID-19 relief fund.

Michael Urie reprises his much-praised performance in "Buyer & Cellar," the solo play that imagines the world of Streisand's basement.

Our culture watch list includes Alfred Molina as painter Mark Rothko in the Tony-winning drama "Red"

In this coronavirus climate, Travis Scott's "Fortnite" collaboration is something of an experiment for our new reality. Games are our new social spaces.

Brush up on your Russian with Opera Santa Barbara's 2019 production of Tchaikovsky's "Eugene Onegin."

Toshi Reagon and her mother, Sweet Honey in the Rock's Bernice Johnson Reagon, adapt Octavia E. Butler's acclaimed novel "Parable of the Sower."

Mark Shakespeare's birthday with a watch party at home. How to see Patrick Stewart in 'Macbeth," Danielle Brooks in "Much Ado About Nothing" and more.

Ariana Grande joins Tony winner Jason Robert Brown and "Wicked" and "Waitress" alum Shoshana Bean in a benefit concert streaming Monday.

Watch the late, great Jessye Norman sing Brahms with the Chamber Music Society of Lincoln Center

San Cha is a queer Latina musician whose new album, 'La Luz de la Esperanza,' is a musical telenovela that reimagines rancheras with a gothic edge.

A city in Denmark held a drive-in concert, with a musician playing onstage outdoors and concertgoers listening in their cars. Could this happen in California?

Celebrate Cinco de Mayo with three livestreams from the Richard and Karen Carpenter Performing Arts Center.

REMEMBER the phrase: "He had a good war"? When we heard it at school it seemed an oxymoron. I recall our history teacher, sensing our confusion, elaborating thus: "For some war was deadly. The bereaved and the disabled never recovered. For some it was a hiatus, a long and frightening test of endurance. Yet some excelled.

THE CORONAVIRUS pandemic is forcing the political elite to finally acknowledge what the general public have known for some time; as a nation we have allowed ourselves to become far too dependent on importing essential goods and cheap labour from across the globe. The financial crisis of 2008 exposed as a myth the claim that globalisation would lead to ever greater prosperity for all. The current crisis has made it crystal clear that globalisation, as well as being bad news for our economy, puts lives at risk.

We answer four questions about the historical accuracy of the Netflix series "Self Made: Inspired by the Life of Madam C.J. Walker."

Iconic singer-songwriter John Prine, who died at age 73, hired Indiana guitarists Jason Wilber and Larry Crane to play in his band.

Ordinary people in their ordinary cars take to the drag strip to get their need for speed.

Batizada de covid-19, a doença é uma infecção respiratória que começa com sintomas como febre e tosse seca e, ao fim de uma semana, pode provocar falta de ar. Cerca de 80% dos casos são leves, e 5%, graves.

Several Hollywood A-listers gave a reading of select parts of the report in New York.

Outside the committee room Wednesday, several lawmakers got to see and be seen.

The author made sense in both the argument put forth as well as in accurately describing the actual policing festive season operations on the ground in the bustling and busy city centre of Durban.

Many educational institutions fall short of having the bare minimum resources to ensure that learners and teachers are safe during school hours.

The DML News App offers the best in news reporting.

The post BREAKING: Founding Father of Rock Who Broke Musical Barriers, Dead at 87 appeared first on Dennis Michael Lynch.

A woman in her 90s living at the Bradford Valley Care Community is the latest coronavirus victim in the region.

Labour laws haven’t changed in our province, but legal experts are already urging B.C. employers to be flexible and reasonable — while warning employees they may not be legally protected if they refuse work during the pandemic.

Support from the Bill & Melinda Gates Foundation has enabled Chatham House to develop a global health security track at the Munich Security Conference (MSC).

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

Invitation Only Research Event

Event participants

Senator Chris Coons, United States Senator, Delaware
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme

7 May 2020 , Volume 96, Number 3

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

The Science Museum is presenting the special Unlocking the Secrets - The Science of Conservation at The Palace Museum exhibition to tie in with the 600th anniversary of the Forbidden City in 2020.

More than 100 artefacts from the Palace Museum collection are being showcased to highlight the application of science and technology in conservation.

They include bronzes, clocks, textiles, thangkas, wood furniture, lacquerware and inlaid works along with ceramics, calligraphy and hand-painted copies of ancient paintings.

The show also presents the Conservation Office’s work by showcasing intriguing restoration cases so that visitors can learn more about the work and skills of conservators as well as their mission to preserve Hong Kong’s heritage assets.

The Science Museum will launch a series of interactive family activities, including demonstrations and workshops conducted by Palace Museum conservators, guided tours featuring theatrical plays and storytelling, and visits to conservation laboratories.

Jointly presented by the Leisure & Cultural Services Department and the Palace Museum, the exhibition will run until March 18 next year.

Call 2732 3232 for enquiries.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.