Publications by authors named "P J Myler"

Article Synopsis
  • Helicobacter pylori is a type 1 carcinogen linked to gastric ulcers and cancer, and research by the Seattle Structural Genomics Center for Infectious Disease focuses on potential treatments targeting this bacterium.
  • The study reports on the purification and crystallization of H. pylori biotin protein ligase (HpBPL), an enzyme that plays a crucial role in important metabolic processes and helps H. pylori thrive in the acidic environment of the stomach.
  • Despite having low sequence identity with similar proteins, HpBPL shares significant structural similarities with Mycobacterium tuberculosis biotin protein ligase, indicating potential for developing inhibitors that could be effective against HpBPL.
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Plasmodium vivax, a significant contributor to global malaria cases, poses an escalating health burden on a substantial portion of the world's population. The increasing spread of P. vivax because of climate change underscores the development of new and rational drug-discovery approaches.

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Griselimycin, a cyclic depsidecapeptide produced by Streptomyces griseus, is a promising lead inhibitor of the sliding clamp component of bacterial DNA polymerases (β-subunit of Escherichia coli DNA pol III). It was previously shown to inhibit the Mycobacterium tuberculosis β-clamp with remarkably high affinity and selectivity - the peptide lacks any interaction with the human sliding clamp. Here, we used a structural genomics approach to address the prospect of broader-spectrum inhibition, in particular of β-clamps from Gram-negative bacterial targets.

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Article Synopsis
  • Trichomonas vaginalis is a one-celled parasite that causes trichomoniasis, the most common nonviral STD worldwide, and it uses mimicry of human proteins to evade the immune system.
  • The parasite produces a protein called TvMIF, which helps it survive stress, boosts prostate cell growth, and triggers inflammation, paralleling the effects of human MIF.
  • Recent studies have revealed the structure of TvMIF, showing it has a similar shape to human versions, suggesting that understanding this protein can aid in developing new drugs.
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Article Synopsis
  • * There is a growing need for alternative treatments due to drug resistance in H. pylori, leading to research at the Seattle Structural Genomics Center for Infectious Disease (SSGCID) into potential drug targets, specifically Glutamyl-tRNA synthetase (GluRS).
  • * The SSGCID has successfully determined the structure of H. pylori GluRS, which shares significant similarities with other bacterial GluRS, presenting opportunities for drug discovery aimed at developing new antibacterials to combat H. pylori infections.
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