Jones & Van Aken monitoring water quality for city of Fairfax
(George Mason University) R. Christian Jones, Professor/Director, Potomac Environmental Research and Education Center, Environmental Science and Policy, and Benoit Van Aken, Associate Professor, Chemistry and Biochemistry, are conducting stream monitoring for the City of Fairfax. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - February 14, 2020 Category: Biology Source Type: news
Structural basis for strand-transfer inhibitor binding to HIV intasomes
The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo–electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have ...
Source: ScienceNOW - February 13, 2020 Category: Science Authors: Passos, D. O., Li, M., Jozwik, I. K., Zhao, X. Z., Santos-Martins, D., Yang, R., Smith, S. J., Jeon, Y., Forli, S., Hughes, S. H., Burke, T. R., Craigie, R., Lyumkis, D. Tags: Biochemistry, Microbiology reports Source Type: news
Structural basis of second-generation HIV integrase inhibitor action and viral resistance
Although second-generation HIV integrase strand-transfer inhibitors (INSTIs) are prescribed throughout the world, the mechanistic basis for the superiority of these drugs is poorly understood. We used single-particle cryo–electron microscopy to visualize the mode of action of the advanced INSTIs dolutegravir and bictegravir at near-atomic resolution. Glutamine-148->histidine (Q148H) and glycine-140->serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. The expanded chemical scaffolds of second-generation c...
Source: ScienceNOW - February 13, 2020 Category: Science Authors: Cook, N. J., Li, W., Berta, D., Badaoui, M., Ballandras-Colas, A., Nans, A., Kotecha, A., Rosta, E., Engelman, A. N., Cherepanov, P. Tags: Biochemistry, Microbiology reports Source Type: news
Researchers look to fungus to shed light on cancer
(Florida State University) A team of Florida State University researchers from the Department of Chemistry and Biochemistry found that a natural product from the fungus Fusicoccum amygdali stabilizes a family of proteins in the cell that mediate important signaling pathways involved in the pathology of cancer and neurological diseases. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - February 11, 2020 Category: Biology Source Type: news
Biochemist Stanley Cohen Dies
The Vanderbilt University professor was awarded a Nobel Prize for his discovery of epidermal growth factor. (Source: The Scientist)
Source: The Scientist - February 10, 2020 Category: Science Tags: News & Opinion Source Type: news
(ETH Zurich) David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof. Baker to identify how algorithmic processes such as de novo design, predict protein structures, protein folding mechanisms, and new protein functions. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - February 7, 2020 Category: Biology Source Type: news
New details on how a viral protein puts the brakes on virus replication
(Colorado State University) Researchers used computational chemistry, biochemistry and virology to uncover new information on how viruses such as West Nile, dengue and Zika replicate. (Source: EurekAlert! - Infectious and Emerging Diseases)
Source: EurekAlert! - Infectious and Emerging Diseases - February 7, 2020 Category: Infectious Diseases Source Type: news
Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations
Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that are activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic class I cytokine receptors in the plasma membrane of living cells by single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation of individual receptor subunits showed ligand-induced dimerization and revealed that the associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic receptor and hyperactive JAK2 mutants promoted ligand-independent dimerization, highlighting the formation of rece...
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Wilmes, S., Hafer, M., Vuorio, J., Tucker, J. A., Winkelmann, H., Löchte, S., Stanly, T. A., Pulgar Prieto, K. D., Poojari, C., Sharma, V., Richter, C. P., Kurre, R., Hubbard, S. R., Garcia, K. C., Moraga, I., Vattulainen, I., Hitchcock, I. S., Pi Tags: Biochemistry r-articles Source Type: news
Structure of an active human histone pre-mRNA 3'-end processing machinery
The 3'-end processing machinery for metazoan replication-dependent histone precursor messenger RNAs (pre-mRNAs) contains the U7 small nuclear ribonucleoprotein and shares the key cleavage module with the canonical cleavage and polyadenylation machinery. We reconstituted an active human histone pre-mRNA processing machinery using 13 recombinant proteins and two RNAs and determined its structure by cryo–electron microscopy. The overall structure is highly asymmetrical and resembles an amphora with one long handle. We captured the pre-mRNA in the active site of the endonuclease, the 73-kilodalton subunit of the cleavage...
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Sun, Y., Zhang, Y., Aik, W. S., Yang, X.-C., Marzluff, W. F., Walz, T., Dominski, Z., Tong, L. Tags: Biochemistry reports Source Type: news
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains
Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense pha...
Source: ScienceNOW - February 6, 2020 Category: Science Authors: Martin, E. W., Holehouse, A. S., Peran, I., Farag, M., Incicco, J. J., Bremer, A., Grace, C. R., Soranno, A., Pappu, R. V., Mittag, T. Tags: Biochemistry reports Source Type: news
Viral Outbreaks Are Here to Stay. This is How Humans Will Fight Back
The year of the rat is off to an ominous start. “We just stay home and don’t go out,” says Mr. Dong. The 33-year-old researcher, who provided only one name, has no other options. He, his wife and their 3-month-old daughter live in Wuhan, the epicenter of an unfolding global health crisis. They’re treating the forced time at home as a holiday, though he says, “this is different than any of them before.” Families like his huddle in their homes, fearful that if they venture out, they will get sick. Since the first cases of a previously unknown pneumonia-like illness emerged in December, Wuh...
Source: TIME: Health - January 30, 2020 Category: Consumer Health News Authors: Alice Park and Charlie Campbell Tags: Uncategorized Source Type: news
Towards better anti-cancer drugs
(Universit ä t Bayreuth) The Bayreuth biochemist Dr. Claus-D. Kuhn and his research team have deciphered how the important human oncogene CDK8 is activated in cells of healthy individuals. Their findings, which have now been published in the journal 'Proceedings of the National Academy of Sciences U.S.A.', explain why promising anti-CDK8 drugs are only effective under laboratory conditions but likely not in humans. Gained results also show a new way of developing CDK8-specific drugs in the future. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - January 28, 2020 Category: Cancer & Oncology Source Type: news
Biochemist Hans Kornberg Dies
An expert on carbohydrate transport, Kornberg contributed to the discovery of several metabolic cycles in microorganisms during his seven-decade career. (Source: The Scientist)
Source: The Scientist - January 27, 2020 Category: Science Tags: News & Opinion Source Type: news
Phase separation provides a mechanism to reduce noise in cells
In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control. (Source: ScienceNOW)
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Klosin, A., Oltsch, F., Harmon, T., Honigmann, A., Jülicher, F., Hyman, A. A., Zechner, C. Tags: Biochemistry, Cell Biology reports Source Type: news
The exposome and health: Where chemistry meets biology
Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The "exposome" concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resol...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Vermeulen, R., Schymanski, E. L., Barabasi, A.-L., Miller, G. W. Tags: Biochemistry, Chemistry special/review Source Type: news
Tracking complex mixtures of chemicals in our changing environment
Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically exposed to thousands of chemicals from various environmental sources through multiple pathways. Environmental chemists and toxicologists have moved beyond detecting and quantifying single chemicals to characterizing complex mixtures of chemicals in indoor and outdoor environments and biological matrices. We highlight analytical and bioanalytical approaches to isolating, characterizing, and tracking groups of chemicals of concern...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Escher, B. I., Stapleton, H. M., Schymanski, E. L. Tags: Biochemistry, Chemistry special/review Source Type: news
A tensile ring drives tissue flows to shape the gastrulating amniote embryo
Tissue morphogenesis is driven by local cellular deformations that are powered by contractile actomyosin networks. How localized forces are transmitted across tissues to shape them at a mesoscopic scale is still unclear. Analyzing gastrulation in entire avian embryos, we show that it is driven by the graded contraction of a large-scale supracellular actomyosin ring at the margin between the embryonic and extraembryonic territories. The propagation of these forces is enabled by a fluid-like response of the epithelial embryonic disk, which depends on cell division. A simple model of fluid motion entrained by a tensile ring q...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Saadaoui, M., Rocancourt, D., Roussel, J., Corson, F., Gros, J. Tags: Biochemistry, Development reports Source Type: news
Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A
Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers—shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions—form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonidentical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguou...
Source: ScienceNOW - January 23, 2020 Category: Science Authors: Reisberg, S. H., Gao, Y., Walker, A. S., Helfrich, E. J. N., Clardy, J., Baran, P. S. Tags: Biochemistry, Chemistry reports Source Type: news
Scientists show we don't need horses to treat diphtheria
(People for the Ethical Treatment of Animals (PETA)) A project taking the first steps towards ending the use of horses to treat diphtheria has succeeded. Funded by the PETA International Science Consortium Ltd. and carried out at the Institute of Biochemistry, Biotechnology, and Bioinformatics at the Technische Universit ä t Braunschweig in Germany, the project created human antibodies capable of blocking the poisonous toxin that causes diphtheria. The results were published Friday in Scientific Reports (a Nature research journal). (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 21, 2020 Category: Biology Source Type: news
Researchers identify a possible cause and treatment for inflammatory bowel disease
(Chinese Academy of Sciences Headquarters) In a study published online in PNAS on Jan. 20, 2020, Prof. SUN Bing's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, in collaboration with Prof. LIU Jie from Huashan Hospital, Fudan University, revealed a new mechanism involved in the pathogenesis of IBD and suggested therapeutic targets for clinical trial. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 21, 2020 Category: International Medicine & Public Health Source Type: news
Look what's inside: Full-body movies from EXPLORER scanner
(University of California - Davis) Positron Emission Tomography, or PET scanning, a technique for tracing metabolic processes in the body, has been widely applied in clinical diagnosis and research spanning physiology, biochemistry and pharmacology. Now researchers at UC Davis and Fudan University, Shanghai have shown how to use an advanced reconstruction method with an ultrasensitive total-body PET scanner to capture real-time videos of blood flow and heart function. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 20, 2020 Category: International Medicine & Public Health Source Type: news
This Strange Microbe May Mark One of Life ’s Great Leaps
A organism living in ocean muck offers clues to the origins of the complex cells of all animals and plants. (Source: NYT Health)
Source: NYT Health - January 15, 2020 Category: Consumer Health News Authors: Carl Zimmer Tags: Microbiology Oceans and Seas Biology and Biochemistry Mitochondria Bacteria Evolution (Biology) Nature (Journal) Masaru K. Nobu Japan Pacific Ocean Arctic Ocean your-feed-science Source Type: news
WPI professor Bruce Bursten honored by ACS for service in field of inorganic chemistry
(Worcester Polytechnic Institute) Bruce Bursten, a chemistry and biochemistry professor at Worcester Polytechnic Institute, has been named by the American Chemical Society to receive the 2020 ACS Award for Distinguished Service in the Advancement of Inorganic Chemistry. The annual award recognizes Bursten for distinguished contributions as a researcher in inorganic electronic structure and bonding, teacher, author and forward-thinking leader. He will be honored in March at a national ACS meeting in Philadelphia. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 15, 2020 Category: Biology Source Type: news
Scientists use stem cells from frogs to build first living robots
Researchers foresee myriad benefits for humanity, but also acknowledge ethical issuesBe warned. If the rise of the robots comes to pass, the apocalypse may be a more squelchy affair than science fiction writers have prepared us for.Researchers in the US have created the first living machines by assembling cells from African clawed frogs into tiny robots that move around under their own steam.Continue reading... (Source: Guardian Unlimited Science)
Source: Guardian Unlimited Science - January 13, 2020 Category: Science Authors: Ian Sample Science editor Tags: Science Robots Research Biochemistry and molecular biology Education Technology World news Source Type: news
Two projects receive NIH grant for breast cancer research
(University of California - Riverside) A research team led by biochemists at the University of California, Riverside, has received a four-year grant from the National Institutes of Health to study breast cancer and the racial disparities in the treatment of the disease. The nearly $1.24 million grant will support two projects: The first will investigate the biology of aggressive luminal B breast cancer; the second will focus on triple-negative breast cancer that is more prevalent in Latina/Hispanic and black women. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - January 8, 2020 Category: Cancer & Oncology Source Type: news
Sir Hans Kornberg obituary
Biochemist who built on the work of Hans Krebs to make key discoveries concerning metabolic cyclesHans Kornberg became a biochemist just at the point, in the mid-20th century, when methods became available to explore how organisms convert food and oxygen into energy and tissue – the combustion engine of life. He was one of the pioneers who identified key participants in such metabolic reactions and measured their effects, knowledge that is fundamental to all of biology.Kornberg, who has died aged 91, was a brilliant bench scientist and never happier than when solving problems in his lab. Yet his genial personality an...
Source: Guardian Unlimited Science - January 7, 2020 Category: Science Authors: Georgina Ferry Tags: Biochemistry and molecular biology Science University of Leicester Higher education University of Cambridge Research Source Type: news
Progesterone from an unexpected source may affect miscarriage risk
(American Society for Biochemistry and Molecular Biology) Progesterone signaling is key to a healthy pregnancy. An Austrian team's research suggests a link between recurrent miscarriage and disrupted progesterone synthesis. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 6, 2020 Category: Biology Source Type: news
Taking the measure of glycans
(American Society for Biochemistry and Molecular Biology) Glycans on antibody drugs can significantly affect their safety and efficacy. A study conducted by NIST investigates how well pharmaceutical and research labs are equipped to measure this important post-translational modification. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 2, 2020 Category: International Medicine & Public Health Source Type: news
TTC5 mediates autoregulation of tubulin via mRNA degradation
Tubulins play crucial roles in cell division, intracellular traffic, and cell shape. Tubulin concentration is autoregulated by feedback control of messenger RNA (mRNA) degradation via an unknown mechanism. We identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers cotranslational degradation of tubulin mRNAs in response to excess soluble tubulin. Structural analysis revealed that TTC5 binds near the ribosome exit tunnel and engages the amino terminus of nascent tubulins. TTC5 mutants incapable of ribosome or nascent tubulin interaction abolished tubulin autoregulation a...
Source: ScienceNOW - January 2, 2020 Category: Science Authors: Lin, Z., Gasic, I., Chandrasekaran, V., Peters, N., Shao, S., Mitchison, T. J., Hegde, R. S. Tags: Biochemistry, Cell Biology reports Source Type: news
Electrostatic control of photoisomerization pathways in proteins
Rotation around a specific bond after photoexcitation is central to vision and emerging opportunities in optogenetics, super-resolution microscopy, and photoactive molecular devices. Competing roles for steric and electrostatic effects that govern bond-specific photoisomerization have been widely discussed, the latter originating from chromophore charge transfer upon excitation. We systematically altered the electrostatic properties of the green fluorescent protein chromophore in a photoswitchable variant, Dronpa2, using amber suppression to introduce electron-donating and electron-withdrawing groups to the phenolate ring....
Source: ScienceNOW - January 2, 2020 Category: Science Authors: Romei, M. G., Lin, C.-Y., Mathews, I. I., Boxer, S. G. Tags: Biochemistry, Chemistry reports Source Type: news
OSU study suggests vitamin D can combat bacterial infection
A new study from Oregon State University reveals yet another potential benefit of vitamin D, which is known to promote calcium absorption and reduce inflammation. OSU scientist Adrian Gombart developed a new model to study vitamin D and found that it can dramatically reduce disease-causing bacteria in skin wounds. The findings were published in the Journal of Steroid Biochemistry and Molecular Biology. The study examines the role of the bioactive form of v itamin D in promoting production of an… (Source: bizjournals.com Health Care:Biotechnology headlines)
Source: bizjournals.com Health Care:Biotechnology headlines - December 30, 2019 Category: Biotechnology Authors: Elizabeth Hayes Source Type: news
OSU study suggests vitamin D can combat bacterial infection
A new study from Oregon State University reveals yet another potential benefit of vitamin D, which is known to promote calcium absorption and reduce inflammation. OSU scientist Adrian Gombart developed a new model to study vitamin D and found that it can dramatically reduce disease-causing bacteria in skin wounds. The findings were published in the Journal of Steroid Biochemistry and Molecular Biology. The study examines the role of the bioactive form of v itamin D in promoting production of an… (Source: bizjournals.com Health Care:Pharmaceuticals headlines)
Source: bizjournals.com Health Care:Pharmaceuticals headlines - December 30, 2019 Category: Pharmaceuticals Authors: Elizabeth Hayes Source Type: news
Targeting cholesterol metabolism in macrophages to eliminate viral infection
(Chinese Academy of Sciences Headquarters) A new study published in Immunity now provides important new information. WANG Hongyan's team from the Center for Excellence in Molecular and Cellular Science, Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences (CAS), in collaboration with Prof. WEI Bin at Shanghai University (the former PI of the Wuhan Institute of Virology of CAS), screened expression levels of multiple enzymes that regulate cholesterol metabolism to better understand how cholesterol metabolites combats infection. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - December 27, 2019 Category: International Medicine & Public Health Source Type: news
Top UCLA news stories of 2019
UCLA began observing its 100th birthday this year and delivered new advances in research, health care, the arts, community service and teaching. These are some of the top stories from UCLA Newsroom in 2019 — those which made news and engaged the community of Bruins and beyond.UCLA Newsroom will resume publishing on Jan. 2, 2020. For more, be sure toperuse the archives and to followUCLA Newsroom on Twitter. UCLA turns 100UCLA ArchiveUCLA from overhead in the 1930s.Founders of UCLA would marvel at their creationIn just 100 years, UCLA has grown into a respected center of learning, research and health ca...
Source: UCLA Newsroom: Health Sciences - December 19, 2019 Category: Universities & Medical Training Source Type: news
The biochemical basis of microRNA targeting efficacy
MicroRNAs (miRNAs) act within Argonaute proteins to guide repression of messenger RNA targets. Although various approaches have provided insight into target recognition, the sparsity of miRNA-target affinity measurements has limited understanding and prediction of targeting efficacy. Here, we adapted RNA bind-n-seq to enable measurement of relative binding affinities between Argonaute-miRNA complexes and all sequences ≤12 nucleotides in length. This approach revealed noncanonical target sites specific to each miRNA, miRNA-specific differences in canonical target-site affinities, and a 100-fold impact of dinucleotides fl...
Source: ScienceNOW - December 19, 2019 Category: Science Authors: McGeary, S. E., Lin, K. S., Shi, C. Y., Pham, T. M., Bisaria, N., Kelley, G. M., Bartel, D. P. Tags: Biochemistry, Molecular Biology, Online Only r-articles Source Type: news
Scorpion venomics: a 2019 overview - Cid-Uribe JI, Veytia-Bucheli JI, Romero-Gutierrez T, Ortiz E, Possani LD.
Introduction: A few scorpions are dangerous to humans. Their medical relevance was the initial driving force for venom research. By classical biochemistry and molecular cloning, several venom peptides and their coding transcripts were characterized,... (Source: SafetyLit)
Source: SafetyLit - December 16, 2019 Category: International Medicine & Public Health Tags: Ergonomics, Human Factors, Anthropometrics, Physiology Source Type: news
Ruth van Heyningen obituary
Biochemist and ophthalmologist whose research concentrated on the formation of cataractsRuth van Heyningen, who has died aged 101, was a pioneering explorer of ophthalmic biochemistry, a field to which she made major contributions after she joined the Nuffield Laboratory of Ophthalmology, at Oxford University, in 1951.Her research, much of which was carried out in collaboration with the laboratory ’s then director,Antoinette (Tony) Pirie, was focused on the lens, in particular the biochemical pathways involved in the formation of cataracts. Tony and Ruth wrote a key book together, Biochemistry of the Eye (1956), whic...
Source: Guardian Unlimited Science - December 15, 2019 Category: Science Authors: Gillian Morriss-Kay Tags: Biochemistry and molecular biology Cataracts People in science University of Oxford Diabetes Wales Source Type: news
Cyrus Chothia obituary
Biochemist whose work was at the cutting edge of the understanding of protein structures, their function and evolutionTaxonomy – the classification of objects according to their relationships to one another – conjures up images of 19th-century amateur naturalists measuring fossils or counting the stamens of flowering plants.The biochemist Cyrus Chothia, who has died aged 77, took a taxonomic approach to research at the cutting edge of molecular biology, organising the bewildering variety of protein structures revealed by techniques such as x-ray crystallography and genome sequencing into coherent family trees.C...
Source: Guardian Unlimited Science - December 12, 2019 Category: Science Authors: Georgina Ferry Tags: Biochemistry and molecular biology Science Yale University Source Type: news
p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). Under some circumstances, p27 is associated with active CDK4, but no mechanism for activation has been described. We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. Surpri...
Source: ScienceNOW - December 12, 2019 Category: Science Authors: Guiley, K. Z., Stevenson, J. W., Lou, K., Barkovich, K. J., Kumarasamy, V., Wijeratne, T. U., Bunch, K. L., Tripathi, S., Knudsen, E. S., Witkiewicz, A. K., Shokat, K. M., Rubin, S. M. Tags: Biochemistry, Medicine, Diseases, Online Only r-articles Source Type: news