A5022917512- Enzyme Structure and Function
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Calcium Carbonate Crystallization and Inhibition
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Computational Drug Discovery Methods
- Protein purification and stability
- Microbial Metabolic Engineering and Bioproduction
- Tuberculosis Research and Epidemiology
- Enzyme Catalysis and Immobilization
- Transgenic Plants and Applications
- Protein Degradation and Inhibitors
- Enzyme Production and Characterization
- Microbial Natural Products and Biosynthesis
- Chemical Synthesis and Analysis
- Bacterial Genetics and Biotechnology
- Plant tissue culture and regeneration
- Biotin and Related Studies
- Peptidase Inhibition and Analysis
- Peroxisome Proliferator-Activated Receptors
- Insect Resistance and Genetics
- Cellular Mechanics and Interactions
- Lysosomal Storage Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
Weizmann Institute of Science
2016-2025
University of Cambridge
2004
Many mineralizing organisms selectively form either calcite or aragonite, two polymorphs of calcium carbonate with very similar crystalline structures. Understanding how these achieve this control has represented a major challenge in the field biomineralization. Macromolecules extracted from aragonitic shell layers some mollusks induced aragonite formation vitro when preadsorbed on substrate β-chitin and silk fibroin. calcitic mainly under same conditions. The results suggest that...
Highlights•A new computational method is used to stabilize five recalcitrant proteins•Designed variants show higher expression and stability with unmodified function•A designed human acetylcholinesterase variant expresses solubly in bacteria•The fully automated implemented on a webserverSummaryUpon heterologous overexpression, many proteins misfold or aggregate, thus resulting low functional yields. Human (hAChE), an enzyme mediating synaptic transmission, typical case of protein that...
Computational design is a test of our understanding enzyme catalysis and means engineering novel, tailor-made enzymes. While the de novo computational catalytically efficient enzymes remains challenge, designed may comprise unique starting points for further optimization by directed evolution. Directed evolution two computationally Kemp eliminases, KE07 KE70, led to low moderately ( k cat / K m values ≤ 5 × 10 4 M -1 s ). Here we describe third design, KE59. Although KE59 was most eliminase...
Proteolysis targeting chimeras (PROTACs) represent an exciting inhibitory modality with many advantages, including substoichiometric degradation of targets. Their scope, though, is still limited to date by the requirement for a sufficiently potent target binder. A solution that proved useful in tackling challenging targets use electrophiles allow irreversible binding target. However, such will negate catalytic nature PROTACs. Reversible covalent PROTACs potentially offer best both worlds....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteractions of various skeletal intracrystalline components with calcite crystalsS. Albeck, J. Aizenberg, L. Addadi, and S. WeinerCite this: Am. Chem. Soc. 1993, 115, 25, 11691–11697Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/ja00078a005https://doi.org/10.1021/ja00078a005research-articleACS PublicationsRequest reuse permissionsArticle...
Protein–protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In present study, we show that interface between proteins built in a modular fashion; each module comprised number closely interacting residues, with few modules. The boundaries modules defined by clustering contact map interface. We mutations one do affect residues located neighboring module. As result, structural and energetic consequences deletion entire...
Control over calcium carbonate deposition in an vitro system containing the major macromolecular components present mollusk shell is shown to depend on presence of a specific protein fraction appropriate microenvironment, this case, silk fibroin adsorbed β-chitin. Experiments with synthetic polypeptides elucidate aspects sequence dependency nucleation aragonite polymorph, here growing nacreous layer bivalve Atrina serrata (note orientation small, newly formed crystals and their merging...
Abstract Assemblies of glycoproteins from within the mineralized tissues sea urchins and mollusks both interact in vitro a similar manner with growing calcite crystals. A protein‐rich fraction, polysaccharide‐rich fraction composed densely glycosylated peptide cores were obtained by chemical enzymatic treatment sea‐urchin spines. Each was partially purified characterized (amino acid composition, FTIR NMR spectroscopy). comparison interactions these fractions crystals shows that...
Natural proteins must both fold into a stable conformation and exert their molecular function. To date, computational design has successfully produced atomically accurate by using so-called "ideal" folds rich in regular secondary structures almost devoid of loops destabilizing elements, such as cavities. Molecular function, binding catalysis, however, often demands nonideal features, including large irregular buried polar interaction networks, which have remained challenging for design....
Antibodies developed for research and clinical applications may exhibit suboptimal stability, expressibility, or affinity. Existing optimization strategies focus on surface mutations, whereas natural affinity maturation also introduces mutations in the antibody core, simultaneously improving stability To systematically map mutational tolerance of an variable fragment (Fv), we performed yeast display applied deep scanning to anti-lysozyme found that many affinity-enhancing clustered at...
Resource5 June 2020Open Access Highly active rubiscos discovered by systematic interrogation of natural sequence diversity Dan Davidi Department Plant and Environmental Sciences, Weizmann Institute Science, Rehovot, Israel Search for more papers this author Melina Shamshoum Zhijun Guo School Biological Nanyang Technological University, Singapore, Singapore Yinon M Bar-On Noam Prywes Molecular Cell Biology, University California, Berkeley, CA, USA Aia Oz Migal Galilee Research Institute,...
Structure determination and functional characterization of macromolecular complexes requires the purification different subunits in large quantities their assembly into a entity. Although isolation structure endogenous has been reported, much progress to be made make this technology easily accessible. Co-expression within hosts such as Escherichia coli insect cells become more amenable, even at level high-throughput projects. As part SPINE (Structural Proteomics In Europe), several...
The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces regulate one another remains unclear. By combining single-molecule magnetic tweezers experiments, Molecular Dynamics simulations, actin-bundling assays, adhesion assembly experiments in live cells, we here describe two-ways allosteric network within as regulator the interaction. We directly observe maturation process upon binding, which reinforces binding at rate...