9rqc

Fragment screening of FosAKP, cryo structure in complex with fragment F2X-entry G02

spinqualitylabelsall models 9rqc, resolution 1.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9rqc is a 2 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.15Å Ligands: DMS, EDO, MN, RCV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A086IRG1_KLEPN Publication Abstract from PubMed Structural insights into protein-ligand interactions are essential for advancing drug development, with macromolecular X-ray crystallography being a cornerstone technique. Commonly X-ray data collection is conducted at cryogenic temperatures to mitigate radiation damage effects. However, this can introduce artifacts not only in the protein conformation but also in protein-ligand interactions. Recent studies highlight the advantages of room-temperature (RT) crystallography in capturing relevant states much closer to physiological temperatures. We have advanced fixed-target serial crystallography to enable high-throughput fragment screening at RT. Here we systematically compare RT fragment screening of the Fosfomycin-resistance protein A from Klebsiella pneumoniae (FosAKP), an enzyme involved in antibiotic resistance, with conventional single crystal data collection at cryogenic temperature (cryo). With RT serial crystallography we achieve resolutions comparable to cryogenic methods and identify a previously unobserved conformational state of the active site, offering additional starting points for drug design. For ligands identified in both screens, temperature does not have an influence on the binding mode of the ligand. But overall, we observe more binders at cryo, both at physiologically relevant and non-relevant sites. With the potential for further automation, RT screening with serial crystallography can advance drug development pipelines by making undiscovered conformations of proteins accessible. Room-temperature X-ray fragment screening with serial crystallography.,Gunther S, Fischer P, Galchenkova M, Falke S, Reinke PYA, Thekku Veedu S, Rodrigues AC, Senst J, Elinjikkal D, Gumprecht L, Meyer J, Chapman HN, Barthelmess M, Meents A Nat Commun. 2025 Oct 13;16(1):9089. doi: 10.1038/s41467-025-64918-6. PMID:41083451 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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