GLY-220 / Glycadia - LARVOL DELTA

Structure-based virtual screening of novel USP5 inhibitors targeting the zinc finger ubiquitin-binding domain. (PubMed, Comput Biol Med) - "The results indicated that the candidate stably binds to the ZnF-UBD of USP5 through crucial interactions with residues ARG221, TRP209, GLY220, ASN207, TYR261, TYR259, and MET266...Moreover, US simulations revealed conformational changes of USP5 during ligand dissociation. These insights provide a valuable foundation for the development of novel inhibitors targeting USP5."

Journal • CNS Disorders • Oncology • Targeted Protein Degradation • UBB • USP5

Substrate DNA Promoting Binding of Mycobacterium tuberculosis MtrA by Facilitating Dimerization and Interpretation of Affinity by Minor Groove Width. (PubMed, Microorganisms) - "Furthermore, docking analysis demonstrated that the structure of the dimer MtrA-DNA (high affinity) was generally consistent with other OmpR family members, while Arg 219 and Gly 220 of the wing domain interacted with the minor groove...Based on the finding of 17 inter-molecule hydrogen bonds identified in the interface of the MtrA dimer, including 8 symmetric complementary ones in the conserved α4-β5-α5 face, we propose that hydrogen bonds should be considered just as important as salt bridges and the hydrophobic patch in the dimerization. Our comprehensive study on a large number of binding fragments with quantitative affinity values provided new insight into the molecular mechanism of dimerization, binding specificity and affinity determination of MtrA and clues for solving the puzzle of how global transcription factors regulate a large quantity of target genes."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Lactate Dehydrogenase Superfamily in Rice and Arabidopsis: Understanding the Molecular Evolution and Structural Diversity. (PubMed, Int J Mol Sci) - "The analysis also highlights the important role of Ser-219, Gly-220 and His-251 in the active site geometry of OsLdh3, OsLdh7 and OsLdh9, respectively. In fact, these three genes have also been found to be highly upregulated under salinity, hypoxia and heavy metal mediated stresses in rice."

Journal

Anti-Fungal Potential of Structurally Diverse FDA-Approved Therapeutics Targeting Secreted Aspartyl Proteinase (SAP) of Candida albicans: an In Silico Drug Repurposing Approach. (PubMed, Appl Biochem Biotechnol) - "The outcome of in silico dynamic simulations depicts that the drugs such as gentamicin, clindamycin, meropenem, metronidazole, and aztreonam emphasize superior binding affinity in terms of demonstrating considerable interaction with the core catalytic residues (Asp 32, Asp86, Asp 218, Gly220, Thr 221, and Thr 222). Data further indicates that the drug gentamicin exhibited best binding affinity of - 14.16 kcal/mol followed by meropenem (- 9.20 kcal/mol), clindamycin (- 9.00 kcal/mol), ciprofloxacin (- 8.95 kcal/mol), and imipenem (- 8.00 kcal/mol). In conclusion, repurposed antibiotics like gentamicin, clindamycin, meropenem, metronidazole, and aztreonam shall be considered an alternate drug of choice for the clinical management of drug resistant candida infections in the near future."

FDA event • Journal • Candidiasis • Infectious Disease

Molecular Docking Analysis of Siddha Formulation Parangipattai Chooranam Against Vaginal Candidiasis. (PubMed, Appl Biochem Biotechnol) - "Results of the present in silico investigation signify that the compounds such as beta-sitosterol, afzelin, apigenin, quercetin and rosmarinic acid ranked first by demonstrating potential binding affinity with active amino acid residues by occupying the respective binding sites (Asp 32, 83 Lys, Asp86, Gly220, Thr221 and Thr222) in comparison with standard drug fluconazole. Vicenin exhibited best binding affinity of - 12.07 kcal/mol followed by beta-sitosterol (- 9.29 kcal/mol), engeletin (- 9.04 kcal/mol), afzelin (- 8.07 kcal/mol) and 4-O-caffeoylquinic acid (- 7.85 kcal/mol) in comparison with fluconazole (- 7.32 kcal/mol). From the results of the present study, it was concluded that the phytochemicals present in the siddha formulation Parangipattai Chooranam reveal significant antifungal activity by inhibiting the target enzyme (SAP) and thereby considered an excellent drug of choice for the clinical management of vaginal candidiasis."

Journal • Candidiasis • Immunology • Infectious Disease • Inflammation • Vaginitis