Wim G. J. Hol
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View article: Jan Drenth (1925–2025)
Jan Drenth (1925–2025) Open
Jan Drenth is remembered.
View article: Suppressor Mutations in Type II Secretion Mutants of Vibrio cholerae: Inactivation of the VesC Protease
Suppressor Mutations in Type II Secretion Mutants of Vibrio cholerae: Inactivation of the VesC Protease Open
Genome-wide transposon mutagenesis has identified the genes encoding the T2SS in Vibrio cholerae as essential for viability, but the reason for this is unclear. Mutants with deletions or insertions in these genes can be isolated, suggestin…
View article: Structure-guided discovery of selective methionyl-tRNA synthetase inhibitors with potent activity against <i>Trypanosoma brucei</i>
Structure-guided discovery of selective methionyl-tRNA synthetase inhibitors with potent activity against <i>Trypanosoma brucei</i> Open
Potent T. brucei methionyl-tRNA synthetase inhibitors built on two novel short and rigid linker systems.
View article: Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of <i>Cryptosporidium</i> Infection
Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of <i>Cryptosporidium</i> Infection Open
Cryptosporidiosis is one of the leading causes of moderate to severe diarrhea in children in low-resource settings. The therapeutic options for cryptosporidiosis are limited to one drug, nitazoxanide, which unfortunately has poor activity …
View article: The crystal structure of the drug target<i>Mycobacterium tuberculosis</i>methionyl-tRNA synthetase in complex with a catalytic intermediate
The crystal structure of the drug target<i>Mycobacterium tuberculosis</i>methionyl-tRNA synthetase in complex with a catalytic intermediate Open
Mycobacterium tuberculosis is a pathogenic bacterial infectious agent that is responsible for approximately 1.5 million human deaths annually. Current treatment requires the long-term administration of multiple medicines with substantial s…
View article: Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry
Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry Open
Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and prote…
View article: Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections
Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections Open
Antibiotic-resistant bacteria are widespread and pose a growing threat to human health. New antibiotics acting by novel mechanisms of action are needed to address this challenge. The bacterial methionyl-tRNA synthetase (MetRS) enzyme is es…
View article: From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis
From Cells to Mice to Target: Characterization of NEU-1053 (SB-443342) and Its Analogues for Treatment of Human African Trypanosomiasis Open
Human African trypanosomiasis is a neglected tropical disease that is lethal if left untreated. Existing therapeutics have limited efficacy and severe associated toxicities. 2-(2-(((3-((1H-Benzo[d]imidazol-2-yl)amino)propyl)amino)methyl)-4…
View article: Development of an Orally Available and Central Nervous System (CNS) Penetrant <i>Toxoplasma gondii</i> Calcium-Dependent Protein Kinase 1 (<i>Tg</i>CDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of <i>Toxoplasmosis</i>
Development of an Orally Available and Central Nervous System (CNS) Penetrant <i>Toxoplasma gondii</i> Calcium-Dependent Protein Kinase 1 (<i>Tg</i>CDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of <i>Toxoplasmosis</i> Open
New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii cal…
View article: Zinc coordination is essential for the function and activity of the type II secretion ATPase EpsE
Zinc coordination is essential for the function and activity of the type II secretion ATPase EpsE Open
The type II secretion system Eps in Vibrio cholerae promotes the extracellular transport of cholera toxin and several hydrolytic enzymes and is a major virulence system in many Gram‐negative pathogens which is structurally related to the t…
View article: 5-Fluoroimidazo[4,5-<i>b</i>]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors
5-Fluoroimidazo[4,5-<i>b</i>]pyridine Is a Privileged Fragment That Conveys Bioavailability to Potent Trypanosomal Methionyl-tRNA Synthetase Inhibitors Open
Fluorination is a well-known strategy for improving the bioavailability of drug molecules. However, its impact on efficacy is not easily predicted. On the basis of inhibitor-bound protein crystal structures, we found a beneficial fluorinat…