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  • Journal article


  • Authors : Nielsen, Jakob Toudahl (2021)

  • NMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple and efficient method that provides unbiased and sensitive aggregate measures of local structure and disorder. It is demonstrated that CheSPI can p...

  • Periodicals (Báo – Tạp chí)


  • Authors : C.J., Markin (2020)

  • Systematic and extensive investigation of enzymes is needed to understand their extraordinary efficiency and meet current challenges in medicine and engineering. We present HT-MEK, a microfluidic platform for high-throughput expression, purification, and characterization of >1500 enzyme variants per experiment. For 1036 mutants of the alkaline phosphatase PafA, we performed >670,000 reactions to determine >5000 kinetic and physical constants for multiple substrates and ...

  • Journal article


  • Authors : Rathinaswamy, Manoj K (2021)

  • The class IB phosphoinositide 3-kinase (PI3K), PI3Kg, is a master regulator of immune cell function, and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kg function is the association of the p110g catalytic subunit to either a p101or p84 regulatory subunit, which mediates activation by G-protein coupled receptors (GPCRs). Here, we report the cryo-EM structure of a heterodimeric PI3Kg complex, p110g-p101. This...

  • Journal article


  • Authors : Kolata, Piotr (2021)

  • Respiratory complex I is a multi-subunit membrane protein complex that reversibly couples NADH oxidation and ubiquinone reduction with proton translocation against trans-membrane potential. Complex I from Escherichia coli is among the best functionally characterizedcomplexes, but its structure remains unknown, hindering further mechanistic studies to understand the enzyme coupling mechanism. Here we describe the single particle cryo electron microscopy (cryo-EM) structure of th...

  • Journal article


  • Authors : Kishikawa, Jun-ichi (2023)

  • The Na+-pumping NADH-ubiquinone oxidoreductase (Na+-NQR) couples electron transfer 3 from NADH to ubiquinone with Na+-pumping, generating an electrochemical Na+ gradient that 4 is essential for energy-consuming reactions in bacteria. Since Na+-NQR is exclusively found in 5 prokaryotes, it is a promising target for highly selective antibiotics. However, the molecular 6 mechanism of inhibition is not well-understood for lack of the atomic structural informa...

  • Journal article


  • Authors : Anderson, Michael J.M. (2023)

  • The adhesion receptor dystroglycan provides a critical mechanical link between the extracellular matrix (ECM) and the actin cytoskeleton to help muscle cells withstand contraction and neural cells maintain the blood brain barrier. Disrupting the link is associated cancer and muscular dystrophy. Proteolysis of dystroglycan by matrix metalloproteinases (MMPs) provides a mechanism to break the mechanical anchor and is amplified in several pathogenic states,&...

  • Ebooks (Sách điện tử)


  • Authors : Madabushi, Sowmya (2023)

  • Puromycin-sensitive aminopeptidase (E.C. 3.4.11.14, UniProt P55786), a zinc 6 metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as 7 well as peptides released from the proteasome, including polyglutamine. We report the 8 crystal structure of PSA at 2.3 Ǻ. Overall, the enzyme adopts a V-shaped architecture 9 with four domains characteristic of the M1 family aminopeptidases, but it is in a less 10...

  • Journal article


  • Authors : Schäfer, an-Hannes (2023)

  • Sphingolipids are structural membrane components that also function in cellular stress 32 responses. The serine palmitoyl-transferase (SPT) catalyzes the rate limiting step in 33 sphingolipid biogenesis. Its activity is tightly regulated through multiple binding part-34 ners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phos-35 phate (PI4P) phosphatase Sac1. The structural organization and regulatory mecha-36 nisms of this complex are not yet understood.

  • Journal article


  • Authors : Shafiei, Alaleh (2023)

  • Frataxin is a 23 KDa mitochondrial iron-binding protein that is involved in biogenesis of iron sulfur clusters. A deficiency in frataxin leads to Friedreich's ataxia, a progressive neurodegenerative disorder. The bacterial ortholog of eukaryotic mitochondrial frataxin, CyaY, is thought to play a role in iron sulfur cluster assembly as an iron supplier, making it an important target for study. Here, we present the first ambient tem...

  • Journal article


  • Authors : Banerjee, Sayanika (2023)

  • Ufmylation, a protein modification by Ubiquitin-like (UBL) protein UFM1, plays a crucial role in several cellular processes including DNA damage response, protein translation and ER homeostasis. To date, little is known how the enzymes responsible for this modification coordinate their action. Here we have studied the details of UFL1 (E3) activity, its binding to UFC1 (E2), and its relation to UBA5 (E1), using a combination of structur...