progesterone (ARG102) / arGentis - LARVOL DELTA

RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains. (PubMed, J Cell Biol) - "Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, to the PM and differentially facilitates the recognition of PS acyl chains...Distribution of these KRAS4B oncogenic mutants favors different nanoscale membrane topography. Thus, RAS G-domains allosterically facilitate membrane lateral distribution."

Journal • Oncology • HRAS • KRAS

In vitro characterization of a novel Arg102 mutation in the ADAMTS13 metalloprotease domain. (PubMed, J Thromb Haemost) - "p.R102S mutation destabilizes the M-D domain interactions, causing impaired ADAMTS13 secretion and activity, which explains the patients' phenotype. Allosteric preactivation of ADAMTS13 remains conserved in the presence of the p.R102S mutation."

Journal • Preclinical • Hematological Disorders • Thrombocytopenic Purpura

A Japanese family with dystonia due to a pathogenic variant in SGCE. (PubMed, Hum Genome Var) - "By using exome analysis, we identified a rare variant in the SGCE gene, NM_003919.3: c.304C > T [Arg102*], in this patient...By allele-specific PCR, we confirmed that the maternally inherited normal allele of SGCE was silenced, and only the paternally inherited variant allele was expressed in this patient. Despite the pathogenicity, identical variants have been recurrently reported in eight independent families from different ethnicities, suggesting recurrent mutations at this mutational hotspot in SGCE."

Journal • CNS Disorders • Dystonia • Movement Disorders

In vitro characterization of a novel Arg102 mutation in the metalloprotease domain of ADAMTS13 (ISTH 2022) - "Secretion of the p.R102S mutant was impaired to 35% of WT secretion. ADAMTS13 activity of purified p.R102S mutant was severely reduced to 12% of WT activity. Although the activity of the p.R102S mutant was low, it could still be 2-fold activated by 17G2."

Preclinical • Hematological Disorders • Thrombocytopenic Purpura

Inside the cracked kernel: establishing the molecular basis of AMG510 and MRTX849 in destabilising KRASG12C mutant switch I and II in cancer treatment. (PubMed, J Biomol Struct Dyn) - "Gly10, Lys16, Thr58, Gly60, Glu62, Glu63, Arg68, Asp69, Met72, His95, Tyr96, Gln99, Arg102 and Val103 interacted prominently with AMG510 and MRTX849. These interactions together with pi-pi stacking, pi-sigma and pi-alkyl interactions induced unfolding of switch I whiles compacting switch II, which could interrupt the binding of effector proteins to these interfaces. These insights present useful atomistic perspectives into the success of AMG510 and MRTX849 which could guide the design of more selective and potent KRAS inhibitors.Communicated by Ramaswamy H. Sarma."

Journal • Oncology • Sarcoma • Solid Tumor • KRAS

Computational Insights Into the Effects of the R190K and N121Q Mutations on the SARS-CoV-2 Spike Complex With Biliverdin. (PubMed, Front Mol Biosci) - "Our simulations indicated that the R190K mutation causes Lys190 to form six hydrogen bonds, guided by Asn99 and Ile101, which brings Lys190 closer to Arg102 and Asn121, thereby weakening the interaction energy between biliverdin and Ile101 as well as Lys190...In addition, N121Q significantly promoted the gate loop deviating to the biliverdin binding site and compressed the site. This work would be useful in understanding the dynamics binding biliverdin to the SARS-CoV-2 spike."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

3D-QSAR, molecular docking, molecular dynamics, and ADME/T analysis of marketed and newly designed flavonoids as inhibitors of Bcl-2 family proteins for targeting U-87 glioblastoma. (PubMed, J Cell Biochem) - "The molecular docking study revealed that BCL-XL has a higher binding affinity with the most active compounds, and the MD simulation showed that some residues of the BH3 domain, such as Phe97, Tyr101, Arg102, and Phe105 create remarkable hydrophobic interactions with the ligands. 3D-QSAR study is a beneficial method to evaluate and design anticancer compounds. Considering the results of the molecular docking study, MD simulation, and ADME/T analysis, the designed compound 54 could be considered as a potential treatment for glioblastoma."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • BCL2 • BCL2L1

Some Dietary Phenolic Compounds Can Activate Thyroid Peroxidase and Inhibit Lipoxygenase-Preliminary Study in the Model Systems. (PubMed, Int J Mol Sci) - "In all cases, an interaction between the inhibitors carboxylic groups and side-chain atoms of Arg102 and Arg139 in an allosteric pocket of LOX was suggested...The highest antiradical activity was found in the case of SA (IC = 0.22 mM). FA/tCA and tCA/SA acted synergistically, whereas antagonism was found for the SA/FA mixture."

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Matriptase cleaves the amyloid-beta peptide 1-42 at Arg-5, Lys-16, and Lys-28. (PubMed, BMC Res Notes) - "The type-II transmembrane extracellular serine protease matriptase was shown to cleave at Arg-102 in the amino-terminal region of the amyloid precursor protein (APP)...Replacement of Arg-601 (Arg-5 in Aβ1-42) by Ala in APP695 prevented matriptase cleavage at this site. Overexpression of matriptase but not its protease-dead mutant in the M17 cells resulted in a significant reduction of the endogenous APP quantity."

Journal • Neuroendocrine Tumor • Oncology • Solid Tumor

Development of sandwich chemiluminescent immunoassay based on an anti-staphylococcal enterotoxin B Nanobody-Alkaline phosphatase fusion protein for detection of staphylococcal enterotoxin B. (PubMed, Anal Chim Acta) - "The arginine residue (Arg) 101, Arg102 and phenylalanine residue (Phe)103 of CDR3 in Nb37 may have contributed to specific binding to form six salt-bridges between these and SEB. In conclusion, in terms of their specificity and sensitivity, the obtained anti-SEB Nb-ALP appears to have the potential to replace chemically labeled probes for the detection of SEB."

Journal

Identification of potential binding pocket on viral oncoprotein HPV16 E6: a promising anti-cancer target for small molecule drug discovery. (PubMed, BMC Mol Cell Biol) - "After determining receptor-ligand interactions between E6 oncoprotein and the six known inhibitors, the amino acids Cys51, Leu50, Arg102, Arg131, Leu67, Val62, and Gln107 were identified to have importance in E6 inhibition. It was generally observed that Leu50 and Cys51 are necessary for high binding affinity with Cys51 being essential for hydrogen bonding. This study identified a potential binding pocket for the E6 inhibitors. Identification of the ligand binding pocket helps to design novel inhibitors of HPV16 E6 oncoprotein as a promising treatment for cervical cancer."

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