Видео

*Talk 1: Plasticity in the multidrug ABC transporter BmrA* *ELI5 Abstract Talk 1: Bacteria and their Tiny Pumps* Imagine bacteria are like tiny houses, and sometimes they get unwanted visitors, like medicine, trying to get inside. Luckily, they have tiny pumps called BmrA that can throw these visitors back out! This talk is about how these pumps work, how they can throw out different kinds of visitors, and how they use their energy efficiently to keep the house clean. *Abstract* This talk explores the mechanisms of drug resistance in bacteria, specifically focusing on the role of BmrA, a multidrug ABC transporter protein. BmrA expels drugs from bacterial cells, contributing to antibiotic resistance. The talk delves into the structure and function of BmrA, highlighting its ability to handle a diverse range of substrates and adapt its conformation to efficiently utilize ATP in nutrient-deficient environments. *Summary* * 0:01 - Introduction to BmrA and its role in multidrug resistance in bacteria, particularly Bacillus subtilis. * 1:25 - Overview of BmrA structure and function, including its alternating access mechanism and ability to transport various substrates. * 4:48 - Discussion of structural studies using X-ray crystallography and cryo-EM, revealing the plasticity of BmrA in both inward and outward facing conformations. * 7:26 - Proposal of a mechanism where BmrA swings between occluded and outward facing conformations, utilizing its plasticity to accommodate diverse substrates and efficiently release them. * 10:20 - Investigation into the impact of substrate binding on ATP binding affinity and the resulting allosteric effects. * 13:48 - Analysis of BmrA's conformational changes using 3D variability analysis and molecular dynamics simulations, demonstrating the reduction in conformational space exploration upon drug binding. * 18:12 - Examination of the functional effects of drug binding on ATPase activity and transport efficiency, revealing an acceleration of ATPase activity and increased transport efficiency at low ATP concentrations. * 21:27 - Postulation of a mechanism where drug binding stabilizes specific conformations, promoting efficient ATP utilization and drug transport in nutrient-deficient environments. *Talk 2: Dissecting the structure of the nickel binding site of HypA•UreE2 complex required for urease maturation* *ELI5 Abstract Talk 2: The Nickel Helper for Tiny Tummies* There are tiny creatures called bacteria that can live in our tummies. Some of them are good, but some can make us sick. These bacteria have a special tool called urease that needs nickel to work. This talk is about two helpers, HypA and UreE, that work together to give nickel to urease so it can do its job. Understanding these helpers might help us find new ways to stop the bad bacteria from making us sick. *Abstract* This talk delves into the structure and function of urease, a nickel-dependent enzyme crucial for the virulence of many bacteria and fungi. The talk focuses on the role of HypA and UreE proteins in the urease maturation pathway, specifically their interaction and formation of a nickel-binding site. Through a combination of techniques such as isothermal titration calorimetry, NMR spectroscopy, and X-ray absorption spectroscopy, the talk elucidates the structural features of this novel nickel-binding site and its implications for urease activation. *Summary* * 30:20 - Introduction to urease, its role in bacterial and fungal virulence, and its dependence on nickel ions for catalytic activity. * 32:28 - Overview of urease structure across different organisms, highlighting the conserved active site containing two nickel ions. * 35:47 - Discussion of potential strategies for targeting urease as a novel antibiotic approach, including inhibiting the enzyme itself or disrupting its maturation pathway. * 36:08 - Introduction to the urease maturation pathway involving UreA, UreB, UreF, UreG, and UreE proteins, with a focus on the role of UreE as a metallochaperone delivering nickel ions. * 37:12 - Exploration of the structure of UreE, its nickel-binding site, and the conformational changes upon nickel binding. * 38:23 - Investigation of the structure of HypA, its nickel-binding site, and the role of specific residues in nickel coordination. * 40:42 - Analysis of the interaction between HypA and UreE, revealing the formation of a high-affinity complex with a novel nickel-binding site not present in the individual proteins. * 43:29 - Investigation into the impact of mutations in nickel-binding residues on the affinity of the HypA•UreE2 complex for nickel, demonstrating a significant decrease in affinity. * 44:57 - Characterization of the nickel-binding site in the HypA•UreE2 complex using X-ray absorption spectroscopy and paramagnetic NMR, revealing a hexacoordinate, high-spin nickel(II) site with ligands from both proteins. i used gemini 1.5 pro Token count 14,211 / 1,048,576

😊все автор фарватер са😊➡вак😅ы😅➡квв😅реванша ын автор книги выпуск смотреть а всё потому ввв😅я😅ща ав😅августа все👤 через если не ВВП ➡е😊Ы й на в в я готов где н ф😊Аваков ➡вннк😅➡ын ав😅 квартиры😅аня спасибо 🙏💕его ес😊школа все Вячеслав ➡вв аа😅😊в😅есть ➡➡➡школе сын ыы😅ш Аваков😅 в😊➡при на🔛🔛 😌➡➡вы ➡😟Ггыавв в😅шо вы 🆗АН-ын ➡в😅➡➡ыы свою ➡➡Аваков пыа😅😅как❓😅есть чтобы ааавр его авы😅евгений вн но но ве😊ах выводы года ВВ ын автор в😅вязание ыы автор книги все сф😊аАпквгв ➡года ВВ Н ➡ввысь 😊???😊😅

This is the second Biennial Sjors has given a talk, we are looking forward to his talk at the Instruct Biennial 2024 in Portugal where the next Bertini awardee will be announced!

19:05 subtomogram averaging is not the only way, you can simply do 0 tilt high dose shot

❣️ 𝘱𝘳𝘰𝘮𝘰𝘴𝘮

Thank you so much for this wonderful and FABULOUS presentation. I felt deeply moved by your incredible dedication to this topic. As a PhD student, I would love to become a post-doc one day, and your encouragement helped so much in my difficult moment. We must work together.

I can't see clearly nd this vid is too helpfull.

Awful sound

Great information in this video 💎! You are late to the party = P r o m o S M!!

Great presentation, very interesting! Are there any further reading sources available to what Dr. Burley said at the end in his "sobering postscript", that maybe the pandemic could have been avoided if inhibiting drugs would have been developed against Nsp5 protease ?

how did you do it can you share with me , thank you

Keeps the good work (Okosun healer) on RUclips, the universe needs to know about your cure a lot of people here in the USA have this virus.

the video image is too poor, you need to fix it more

I got healed from hsv1/2 introduction and the response of #DrMba when I saw recommendations, am so happy that I'm free...

#Doctorojie herbs cured my herpes thanks doc <3 <3

We have a protein sample, which is being used at different temperatures and pH and we are seeing vertical (i.e., molar ellipticity magnitude) shifts in the CD spectrum. It cannot be due to concentration because it is all the exact same sample. We did a 222nm/208 and for the most part there is linearity across temperatures at pH 7. However, at lower pH the 222nm/208nm plots show kinks at the higher temps, but there is no "directionality"/correlation between the magnitude of the vertical shift and temperature (or pH). The shifts seem quite random. Any advice? Suggestions? Should we do WSD to be able to say "There is no significant change in secondary structure?"

Can you post the link for the normalization software that is at 16:45?

This was extremely helpful! Could you perhaps recommend extra resources that might be helpful in learning this technique and data interpretation

Is this opportunity available for non-European people..?