BEGIN:VCALENDAR VERSION:2.0 PRODID:-//CERN//INDICO//EN BEGIN:VEVENT SUMMARY:Structural basis of specific lysine transport by Pseudomonas aerug inosa permease LysP DTSTART;VALUE=DATE-TIME:20260327T114000Z DTEND;VALUE=DATE-TIME:20260327T120000Z DTSTAMP;VALUE=DATE-TIME:20260426T003809Z UID:indico-contribution-802-10350@events.saip.org.za DESCRIPTION:Speakers: Emmanuel Nji (BioStruct-Africa)\nUnder conditions o f extreme acidity\, the lysine-specific permease\, LysP\, not only mediate s the import of L-lysine it also interacts with the transcriptional regula tor\, CadC\, to activate expression of the cadAB operon. This operon encod es the lysine decarboxylase\, CadA\, which converts lysine to cadaverine w hile consuming a cytoplasmic proton\, and the antiporter\, CadB\, which ex ports protonated cadaverine in exchange for extracellular lysine. Together \, these processes contribute to cytoplasmic pH homeostasis and support ba cterial acid resistance - a mechanism essential for the survival of pathog enic bacteria in acidic host environments. Here\, we present the cryo-EM s tructure of LysP from Pseudomonas aeruginosa in an inward-occluded conform ation (3.2–5.3 Å resolution)\, bound to L-lysine and a nanobody. L-Ly sine is coordinated by hydrophobic contacts\, cation–π interactions\, a nd by hydrogen bonding mostly with polar uncharged residues. Reconstitutio n of LysP into proteoliposomes confirms specific L-lysine transport\, whic h is competitively inhibited by L-4-thialysine. These findings provide a s tructural framework for understanding selective lysine recognition and inh ibition\, with implications for antibacterial drug design.\n\nhttps://even ts.saip.org.za/event/272/contributions/10350/ LOCATION: URL:https://events.saip.org.za/event/272/contributions/10350/ END:VEVENT BEGIN:VEVENT SUMMARY:Structural insights into the DDX11 helicase DTSTART;VALUE=DATE-TIME:20260326T110000Z DTEND;VALUE=DATE-TIME:20260326T113000Z DTSTAMP;VALUE=DATE-TIME:20260426T003809Z UID:indico-contribution-802-10324@events.saip.org.za DESCRIPTION:Speakers: Silvia Onesti (N/A)\nHelicases are essential and ubi quitous enzymes\, playing a key role in a variety of processes in DNA and RNA metabolism. A subset of helicases play specialised and specific functi ons by resolving/remodelling a variety of atypical DNA structures\, such a s G-quadruplexes\, triplexes\, Holliday junctions\, as well as displacemen t loops (D-loops and R-loops): among those a major role is played by the F eS family. Helicases containing FeS-clusters are ubiquitous but their exac t mechanism of action is poorly understood\; no structural information is available for some medically-relevant members of the family\, like FANCJ\, DDX11 and RTEL1.The combination of the intrinsic conformational flexibili ty\, FeS cluster lability and size makes them challenging targets for stru ctural biology.\n\nDDX11 plays an important role in sister-chromatid cohes ion\, associates with the replisome and is involved in processing non-cano nical nucleic acid structures. We have expressed and purified the human pr otein with an intact FeS cluster and carried out an extensive biochemical characterization. We have collected Cryo-EM data for the protein alone and in complex with a DNA fork: the apo structure is being refined at 3.5 Å resolution and a preliminary 5 Å structure in complex with a DNA fork has been determined. We can clearly see the path of the DNA fork bound to the helicase including the double helix\, and the 5’ single strand across t he motor domains. Interestingly\, in same regions the structure differs si gnificantly from the AlphaFold model. \nThese structures provide an essent ial framework to better understand the role of these enzymes.\n\nhttps://e vents.saip.org.za/event/272/contributions/10324/ LOCATION: URL:https://events.saip.org.za/event/272/contributions/10324/ END:VEVENT BEGIN:VEVENT SUMMARY:Structure-Based Discovery of KRAS Inhibitors DTSTART;VALUE=DATE-TIME:20260327T123000Z DTEND;VALUE=DATE-TIME:20260327T125000Z DTSTAMP;VALUE=DATE-TIME:20260426T003809Z UID:indico-contribution-802-10319@events.saip.org.za DESCRIPTION:Speakers: Amanuel Getahun Addis (Bahir Dar University)\n**Abst ract**\nKristen rat sarcoma (KRAS) is an oncogene responsible for almost 2 0% of all human cancers and over 90% of pancreatic ductal adenocarcinoma. To date\, only two covalent drugs are approved by the United States food and drug administration (FDA) for the treatment of KRAS G12C related canc ers. However\, their effectiveness is limited in cancers driven by non-G12 C KRAS mutations as they rely on covalent bonding to the mutant Cys12. On top of that\, the emergence of resistance to allele-specific inhibitors h as shifted substantial effort toward developing noncovalent KRAS inhibitor s. As a result\, several noncovalent inhibitors are in clinical trials\, yet none has been approved for market use\, underscoring the need for new inhibitors. In this study\, we reported small molecules that show a promi sing micromolar anti-proliferation activity against pancreatic cancer cell lines. The investigated compounds are mainly amine-containing heterocycle s with scaffolds that are distinct from those found in existing drugs or l ead molecules.The molecules were identified through a structure-based drug design campaign on a physicochemically tailored 3D ligand library against switch II pocket of KRAS mutants. Based on their micromolar activity\, ex tensive interactions in predicted binding modes\, and analyses of structur al and physicochemical features\, we propose that these active hits can se rve as a starting point for the future characterization and optimization o f pan-KRAS inhibitors with broad efficacy. Moreover\, our work demonstrate s the proof of concept for using virtual screening in noncovalent drug dis covery to benefit from abundant 3D structures of drug-like molecules and t he growing database of experimental protein structures\, especially when c omputational resources are limited.\n\n**Keywords**: KRAS drug discovery\, virtual screening\, molecular docking\, cell growth assay\n\n* *Correspon dence to*: amanuel.getahun@bdu.edu.et\n\nhttps://events.saip.org.za/event/ 272/contributions/10319/ LOCATION: URL:https://events.saip.org.za/event/272/contributions/10319/ END:VEVENT END:VCALENDAR