Thomas E. Edwards
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Crystal structure of a short-chain dehydrogenase from <i>Brucella ovis</i> with apo and coenzyme NAD <sup>+</sup> -bound protomer chains Open
Short-chain dehydrogenases (SDRs) are a family of NAD(P)-dependent enzymes involved in redox reactions, specifically carbonyl–alcohol reductions. Here, we report the apo and NAD + -bound structures of an SDR from the pathogenic organism Br…
Architecture of <i>Pseudomonas aeruginosa</i> glutamyl-tRNA synthetase defines a subfamily of dimeric class Ib aminoacyl-tRNA synthetases Open
The aminoacyl-tRNA synthetases (AaRSs) are an ancient family of structurally diverse enzymes that are divided into two major classes. The functionalities of most AaRSs are inextricably linked to their oligomeric states. While GluRSs were p…
Crystal structure of a short-chain dehydrogenase from <i>Burkholderia cenocepacia</i> J2315 in complex with NADP <sup>+</sup> and benzoic acid. Corrigendum Open
The name of one of the authors in the article by Belfon et al. [(2024), Acta Cryst. F 80 , 348–355] is corrected.
Exquisite selectivity of griselimycin extends to beta subunit of DNA polymerases from Gram-negative bacterial pathogens Open
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 inh…
Structure of <i>Plasmodium vivax</i> <i>N</i>-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy Open
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 develop…
Crystal structure of a short-chain dehydrogenase from <i>Burkholderia cenocepacia</i> J2315 in complex with NADP <sup>+</sup> and benzoic acid Open
Burkholderia cenocepacia is an opportunistic human pathogen that can cause lethal infections in immunocompromised individuals, particularly those with cystic fibrosis. As such, there is a critical need to identify and characterize the stru…
View article: Crystal structure of glutamyl-tRNA synthetase from <i>Helicobacter pylori</i>
Crystal structure of glutamyl-tRNA synthetase from <i>Helicobacter pylori</i> Open
Helicobacter pylori is one of the most common bacterial infections; over two-thirds of the world's population is infected by early childhood. Persistent H. pylori infection results in gastric ulcers and cancers. Due to drug resistance, the…
Ternary structure of <i>Plasmodium vivax</i> <i>N</i>-myristoyltransferase with myristoyl-CoA and inhibitor IMP-0001173 Open
Plasmodium vivax is a major cause of malaria, which poses an increased health burden on approximately one third of the world's population due to climate change. Primaquine, the preferred treatment for P. vivax malaria, is contraindicated i…
Structural and functional characterization of FabG4 from <i>Mycolicibacterium smegmatis</i> Open
The rise in antimicrobial resistance is a global health crisis and necessitates the development of novel strategies to treat infections. For example, in 2022 tuberculosis (TB) was the second leading infectious killer after COVID-19, with m…
Crystal structure and biophysical characterization of IspD from <i>Burkholderia thailandensis</i> and <i>Mycobacterium paratuberculosis</i> Open
The methylerythritol phosphate (MEP) pathway is a metabolic pathway that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, the MEP pathway is present in bacteria and not in mammals, which makes the …
Chimeric antigens displaying GPR65 extracellular loops on a soluble scaffold enabled the discovery of antibodies, which recognized native receptor Open
GPR65 is a proton-sensing G-protein coupled receptor associated with multiple immune-mediated inflammatory diseases, whose function is relatively poorly understood. With few reagents commercially available to probe the biology of receptor,…
Chimeric antigens displaying GPR65 extracellular loops on a soluble scaffold enabled the discovery of antibodies, which recognized native receptor Open
GPR65 is a proton-sensing G-protein coupled receptor associated with multiple immune-mediated inflammatory diseases, whose function is relatively poorly understood. With few reagents commercially available to probe the biology of receptor,…
Characterization of a family I inorganic pyrophosphatase from <i>Legionella pneumophila</i> Philadelphia 1 Open
Inorganic pyrophosphate (PP i ) is generated as an intermediate or byproduct of many fundamental metabolic pathways, including DNA/RNA synthesis. The intracellular concentration of PP i must be regulated as buildup can inhibit many critica…
Structure-Guided Discovery of N<sup>5</sup>-CAIR Mutase Inhibitors Open
Because purine nucleotides are essential for all life, differences between how microbes and humans metabolize purines can be exploited for the development of antimicrobial therapies. While humans biosynthesize purine nucleotides in a 10-st…
New therapeutic strategies for <i>Mycobacterium abscessus</i> pulmonary diseases – untapping the mycolic acid pathway Open
There is an increasing body of evidence validating the mycolic acid pathway as an attractive drug target to be further exploited for M. abscessus lung disease treatments. The NITD-916 studies provide a proof-of-concept that direct inhibito…
<i>In Vitro</i> and <i>In Vivo</i> Efficacy of NITD-916 against Mycobacterium fortuitum Open
Mycobacterium fortuitum represents one of the most clinically relevant rapid-growing mycobacterial species. Treatments are complex due to antibiotic resistance and to severe side effects of effective drugs, prolonged time of treatment, and…
View article: Mineral Detection of Neutrinos and Dark Matter. A Whitepaper
Mineral Detection of Neutrinos and Dark Matter. A Whitepaper Open
Minerals are solid state nuclear track detectors - nuclear recoils in a mineral leave latent damage to the crystal structure. Depending on the mineral and its temperature, the damage features are retained in the material from minutes (in l…
Efficacy and Mode of Action of a Direct Inhibitor of <i>Mycobacterium abscessus</i> InhA Open
There is an unmet medical need for effective treatments against Mycobacterium abscessus pulmonary infections, to which cystic fibrosis (CF) patients are particularly vulnerable. Recent studies showed that the antitubercular drug isoniazid …
View article: Structure–Kinetic Relationship Studies for the Development of Long Residence Time LpxC Inhibitors
Structure–Kinetic Relationship Studies for the Development of Long Residence Time LpxC Inhibitors Open
UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a promising drug target in Gram-negative bacteria. Previously, we described a correlation between the residence time of inhibitors on Pseudomonas aeruginosa LpxC (paL…
View article: Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography
Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography Open
E-cadherin adhesion is regulated at the cell surface, a process that can be replicated by activating antibodies. We use cryo-electron microscopy (EM) and X-ray crystallography to examine functional states of the cadherin adhesive dimer. Th…
Structural characterization of aspartate-semialdehyde dehydrogenase from Pseudomonas aeruginosa and Neisseria gonorrhoeae Open
Gonorrhoea infection rates and the risk of infection from opportunistic pathogens including P. aeruginosa have both risen globally, in part due to increasing broad-spectrum antibiotic resistance. Development of new antimicrobial drugs is n…
View article: Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody
Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody Open
E-cadherin (Ecad) is an essential cell–cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Us…
X-ray crystallographic studies of pri-miR-21 Open
Micro RNA (miRNA) are noncoding RNAs that are involved in gene silencing and transcriptional regulation.microRNAs are transcribed as long stem-loop structures (pri-miRNA).These molecules undergo double-stranded cleavage by the enzyme drosh…
View article: Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody
Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody Open
E-cadherin (Ecad) is an essential cell-cell adhesion protein with tumor suppression properties. The adhesive state of Ecad can be modified by the monoclonal antibody 19A11, which has potential applications in reducing cancer metastasis. Us…
Structures of plasmepsin X from <i>Plasmodium falciparum</i> reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme Open
Plasmodium falciparum plasmepsin X ( Pf PMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of…
Structures of plasmepsin X from <i>P. falciparum</i> reveal a novel inactivation mechanism of the zymogen and molecular basis for binding of inhibitors in mature enzyme Open
Plasmodium falciparum plasmepsin X ( Pf PMX), involved in the invasion and egress of this deadliest malarial parasite, is essential for its survival and hence considered as an important drug target. We report the first crystal structure of…