A5029772826- Organophosphorus compounds synthesis
- Synthesis and Reactivity of Sulfur-Containing Compounds
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Phosphorus compounds and reactions
- Microtubule and mitosis dynamics
- Asymmetric Synthesis and Catalysis
- Crystal structures of chemical compounds
- Photosynthetic Processes and Mechanisms
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Advanced NMR Techniques and Applications
- Crystallography and molecular interactions
- Ubiquitin and proteasome pathways
- Analytical Chemistry and Chromatography
- Chemical Synthesis and Reactions
- Synthetic Organic Chemistry Methods
- Synthesis and characterization of novel inorganic/organometallic compounds
- Molecular spectroscopy and chirality
- DNA and Nucleic Acid Chemistry
- 14-3-3 protein interactions
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
- Synthesis and Characterization of Heterocyclic Compounds
- Asymmetric Hydrogenation and Catalysis
ETH Zurich
2022-2025
Rockefeller University
2019-2023
Jacksonville College
2023
WinnMed
2023
Mayo Clinic in Florida
2023
University of Wrocław
2023
Toronto Metropolitan University
2021
Institute of Ceramics and Building Materials
2006-2019
McGill University
2011-2016
University of Łódź
1994-2011
Abstract γ-Tubulin ring complex (γ-TuRC) is the major microtubule-nucleating factor. After nucleation, microtubules can be released from γ-TuRC and stabilized by other proteins, such as CAMSAPs, but biochemical cross-talk between minus-end regulation pathways poorly understood. Here we reconstituted this process in vitro using purified components. We found that all CAMSAPs could bind to minus ends of γ-TuRC-attached microtubules. CAMSAP2 CAMSAP3, which decorate stabilize growing not tracking...
Microtubule nucleation is templated by the γ-tubulin ring complex (γ-TuRC), but its structure deviates from geometry of α-/β-tubulin in microtubule, explaining complex's poor nucleating activity. Several proteins may activate γ-TuRC, mechanisms underlying activation are not known. Here, we determined porcine γ-TuRC purified using CDK5RAP2's centrosomin motif 1 (CM1). We identified an unexpected conformation bound to multiple protein modules containing MZT2, GCP2, and CDK5RAP2, resulting a...
Microtubule organization depends on the γ-tubulin ring complex (γ-TuRC), a ∼2.3-MDa nucleation factor comprising an asymmetric assembly of and GCP2-GCP6. However, it is currently unclear how γ-TuRC-associated microproteins MZT1 MZT2 contribute to structure regulation holocomplex. Here, we report cryo-EM structures in context native human γ-TuRC. forms two subcomplexes with N-terminal α-helical domains GCP3 or GCP6 (GCP-NHDs) within γ-TuRC "lumenal bridge." We determine X-ray recombinant...
New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS−Oligos via oxathiaphospholane approach. These monomers their 2-oxo analogues "chimeric" constructs (PS/PO−Oligos) possessing phosphate P-stereodefined phosphorothioate internucleotide linkages. The yield a single coupling step is approximately 92−95%, resulting oligomers are free nucleobase- sugar-phosphorothioate...
The formation of cellular microtubule networks is regulated by the γ-tubulin ring complex (γ-TuRC). This ∼2.3 MD assembly >31 proteins includes and GCP2-6, as well MZT1 an actin-like protein in a “lumenal bridge” (LB). challenge reconstituting γ-TuRC has limited dissections its function. Here, we report biochemical reconstitution human (γ-TuRC-GFP) ∼35 S that nucleates microtubules vitro. In addition, generate subcomplex, γ-TuRCΔLB-GFP, which lacks actin. We show γ-TuRCΔLB-GFP guanine...
Although the α-helical secondary structure of proteins is well-defined, exact causes and structures helical kinks are not. This especially important for transmembrane (TM) helices integral membrane proteins, many which contain providing functional diversity despite predominantly structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine axes alongside positions angles kinks. Analysis all nonredundant high-resolution protein (842 TM from 205 polypeptide chains)...
A compound that binds to tubulin in an unusual way has superior antitumor efficacy and safety a distinctive impact on microtubule curvature dynamics.
The γ-tubulin ring complex (γ-TuRC) has essential roles in centrosomal and non-centrosomal microtubule organization during vertebrate mitosis. While there have been important advances understanding γ-TuRC-dependent nucleation, γ-TuRC capping of minus-ends remains poorly characterized. Here, we utilized biochemical reconstitutions cellular assays to characterize the human γ-TuRC's activity. Single filament showed that remained associated with a nucleated for tens minutes. In contrast, caps at...
Aurora-B is the kinase subunit of Chromosome Passenger Complex (CPC), a key regulator mitotic progression that corrects improper kinetochore attachments and establishes spindle midzone. Recent work has demonstrated CPC microtubule-associated protein complex microtubules are able to activate by contributing auto-phosphorylation in trans. activation thought occur when local concentration high, as occurs enriched at centromeres. It not clear, however, whether distributed binding large...
The centrosome-associated proteins Ninein (Nin) and Ninein-like protein (Nlp) play significant roles in microtubule stability, nucleation anchoring at the centrosome mammalian cells. Here, we investigate Blastoderm specific gene 25D (Bsg25D), which encodes only Drosophila that is closely related to Nin Nlp. In early embryos, find Bsg25D mRNA are associated with centrosomes astral microtubules. We show sequences within coding region 3'UTR of mRNAs important for proper localization this...
Addition of α-phosphonate carbanions to (S)-sulfinimines 1 affords N-sulfinyl β-aminophosphonates 2 in a diastereoisomeric ratio from 5:1 10:1; the major diastereoisomers 2, after separation, are converted corresponding 3 or (+)-β-amino-β-phenylethane phosphonic acid 4, whose absolute configuration was established as (R) by X-ray crystallography.
Summary Microtubule nucleation in cells is templated by the γ-tubulin ring complex (γ-TuRC), a 2.3 MDa multiprotein assembly concentrated at microtubule organizing centers (MTOCs). Current γ-TuRC structures exhibit an open conformation that deviates from geometry of α/β-tubulin microtubule, potentially explaining their low vitro microtubule-nucleating activity. Several proteins have been proposed to activate γ-TuRC, but mechanisms underlying activation are not known. Here, we isolated...
α/β-tubulin heterodimers, which can harbor diverse isotypes and post-translational modifications, polymerize into microtubules that are fundamental to many cellular processes. Due long-standing challenges in generating recombinant tubulin, however, it has been difficult examine the properties of specific tubulin isotypes. Here, we provide a protocol for purifying milligrams affinity tag-free, isotypically pure tubulin. Our method be applicable any interest, opening door dissecting how...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiastereofacial selectivity in 1,3-dipolar cycloaddition to methylphenylvinylphosphine oxideAlberto Brandi, Patrizia Cannavo, K. Michal Pietrusiewicz, Maria Zablocka, and WieczorekCite this: J. Org. Chem. 1989, 54, 13, 3073–3077Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/jo00274a022https://doi.org/10.1021/jo00274a022research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational Preference in 1,3-Dithianes Containing 2-Phosphoryl, -(thiophosphoryl), and -(selenophosphoryl) groups. Chemical Crystallographic Implications of the Nature Anomeric EffectMarian Mikolajczyk, Piotr P. Graczyk, Michal W. WieczorekCite this: J. Org. Chem. 1994, 59, 7, 1672–1693Publication Date (Print):April 1, 1994Publication History Published online1 May 2002Published inissue 1 April...
Abstract Prochiral bis(cyanomethyl) sulfoxide has been successfully transformed into the corresponding optically active mono amide and acid with enantiomeric excesses ranging from low (10 %) to very high (up 99 using a broad spectrum of nitrile‐hydrolysing enzymes.
The complete desymmetrization of optically inactive meso-tartaric acid with (+)-camphor in the presence trimethyl orthoformate is key to synthesis both enantiomers cyclopentenoid isoterrein enantiomerically pure form.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Stereospecific Method of Synthesis [Sp]- and [Rp]-Dinucleoside-(3',5') MethanephosphonatesLucyna A. Wozniak, Jaroslaw Pyzowski, Michal Wieczorek, Wojciech J. StecCite this: Org. Chem. 1994, 59, 20, 5843–5846Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://doi.org/10.1021/jo00099a001Request reuse permissionsArticle Views121Altmetric-Citations29LEARN ABOUT THESE...
The crystal and molecular structure of diastereomerically pure N4-benzoyl-2'-deoxycytidine 3'-O-(Se-methyl methanephosphonoselenolate (FAST-eluted) (4, R = H, B CBz) 5'-O-pixylthymidine 3'-O-(S-methyl methanephosphonothiolate (5) have been elucidated by X-ray crystallography. absolute configuration at the phosphorus atom in both compounds is SP. Each FAST-4' (R DMT, FAST-5 Px, Thy) process DBU/LiCl-assisted condensation with 3'-O-acetyl-N4-benzoylcytidine 3'-O-acetylthymidine gave after...