1H, 15N and 13C backbone and side-chain resonance assignments of Amblyomin-X Kunitz domain

1H, 15N, 13C backbone resonance assignment of Escherichia coli AlkB in complex with Zn(II) and α-ketoglutarate

Protein and nucleic acid alkylation are important genetic and epigenetic modifications. The dynamic balance between alkylation and dealkylation is regulated by distinct sets of enzymes and is essential for maintaining genomic stability. Escherichia coli AlkB is a member of the Alkylation B (AlkB) family of dioxygenases that dealkylates a wide range of nucleic acid substrates in E. coli, thereby playing a crucial role in cellular repair processes and epigenetic regulation. Here, we report the backbone 1H, 15N, 13C chemical shift assignment of E. coli AlkB in complex with Zn2+ and α-ketoglutarate. Experiments were acquired at 20 °C by heteronuclear multidimensional NMR spectroscopy. Collectively, 91% of all 13C, 15N and 1H backbone resonances of Alkb were assigned, with 182 out of a possible 200 residues assigned in the 1H–15N TROSY spectrum. Using the program TALOS + , a secondary structure prediction was generated from the assigned backbone resonances that is consistent with the previously reported X-ray structure of the enzyme. The reported assignment will permit investigations of the protein structural dynamics anticipated to provide crucial insight regarding fundamental aspects in the recognition and enzyme regulation processes.

Structural and Biophysical Characterization of Aminobenzo[d]isothiazole 1,1-Dioxide SOS1 Ligands

SOS1 is a guanine nucleotide exchange factor that promotes KRAS activation by catalyzing GDP release and GTP loading, making SOS1-mediated nucleotide exchange an attractive therapeutic target in KRAS-driven cancers. Herein, we report the synthesis, biophysical characterization, and structural analysis of aminobenzo[d]isothiazole 1,1-dioxide SOS1 ligands. Compound 6f engaged SOS1 with a KD of 570 nM by microscale thermophoresis, supported by surface plasmon resonance. X-ray crystal structures of SOS1 bound to compounds 6b and 6f refined previous binding hypotheses regarding pocket engagement. Rather than being dominated by sulfone-mediated contacts, SOS1 recognition is primarily driven by hydrophobic and aromatic packing within the canonical pocket, a conserved ligand NH hydrogen bond to Asn879, and π-π stacking with Tyr884, recapitulating key features of BI-3406 binding. Comparative analysis further delineates vector requirements for productive engagement of KRAS-facing regions, providing a structure-based framework for future optimization of aminobenzo[d]isothiazole 1,1-dioxide SOS1 ligands.

Distinct Molten-Globule Conformations in an Interacting Protein Domain Resolved by 19F NMR of Fluoroproline Residues.

This study illustrates how subtle residue-localized conformational bias can affect the overall protein conformational dynamics influencing protein-protein interactions that are important for cellular functions and related to diseases.

Synthesis, Structural Elucidation and DFT Studies of Novel Coumarin Derivative with Docking, ADMET Analysis and Antibacterial Activities

NMR assignments and secondary structure analysis of the human 5MP1 C-terminal domain

Solution Structures of Glycosaminoglycan-bound CXCL8 Complexes Determined by Small-Angle X-Ray Scattering (SAXS).

Together, these studies establish how GAGs are organized in the CXCL8-bound complex and highlight the value of complementary low-resolution structural methods for characterizing GAG-protein complexes.