| Structural Insights into Mechanisms of Catalysis and Inhibition in Norwalk Virus Polymerase |
Outbreaks of Norwalk virus are notorious for causing severe dehydration due to vomiting and diarrhea. The currently untreatable bug belongs to a superfamily of viruses that stores their genetic code as RNA. Researchers at the University of Calgary used high-resolution data from the 08ID-1 beamline to determine the structure the Norwalk virus polymerase in various complexed states. The information is crucial to better understand viral replication and for drug development. |
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Original Publication | CLS Science Highlights |
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J. Biol. Chem., Vol. 283, Issue 12, 7705-7712, March 21, 2008
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| Structure–Activity Relationships of C6-Uridine Derivatives Targeting Plasmodia Orotidine Monophosphate Decarboxylase |
Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug resistance. In Plasmodia, orotidine 5’-monophosphate decarboxylase (ODCase) is an essential enzyme for the de novo synthesis of uridine 5’-monophosphate. Impairing ODCase in these pathogens is a promising strategy to develop novel classes of therapeutics. Researchers from the group of Dr. E. Pai (University of Toronto) used data from the 08ID-1 beamline to investigate the structure–activity relationships of various novel inhibitors of ODCase. |
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Original Publication |
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J. Med. Chem., 51 (3), 439–448, 2008. 10.1021/jm7010673
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| Characterization of 3-ketosteroid 9alpha -hydroxylase, a Rieske oxygenase in the cholesterol degradation pathway of Mycobacterium tuberculosis |
Mycobacterium tuberculosis (Mtb), the bacteria that causes tuberculosis, is a resilient organism that can only be effectively treated by a lengthy course of multiple drugs. Mtb is able to survive by harvesting the cholesterol stored in white blood cells. Researchers from the University of British Columbia used the 08ID-1 beamline to collect data about the strucuture of KshAB, one of the enzymes used to break down cholesterol. This structural information can be used to design drugs to interfere with the enzyme and develop improved drugs for the treatment of tuberculosis. |
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Original Publication | CLS Science Highlights |
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J. Biol. Chem., Vol.284(15), pp. 9937-9946. 2009
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| Ferritin is Used for Iron Storage in Bloom-Forming Marine Pennate Diatoms |
Diatoms are unicellular phytoplankton that account for much of the primary productivity in the world's oceans. The growth and population size of diatoms is dependent on the availability of iron. Using data from the 08ID-1 beamline, researchers from the University of British Columbia determined that pennate diatoms are able to produce an iron-concentrating protein, ferritin, to store iron and thrive in areas that are usually iron-poor. |
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Original Publication | CLS Science Highlights |
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Nature 457, pp. 467-470. DOI: 10.1038/nature07539. 2009
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| Structural Basis of Substrate Binding to UDP-galactopyranose Mutase |
The need for novel antibiotics is increasingly pressing in the face of the rising threat of bacteria resistant to existing drugs. One approach for such antibiotics is to target the building blocks of bacterial cell walls. One such component is lipopolysaccharide, formed from sugars that are in turn produced using the enzyme UDP-galactopyranose mutase (UGM). Researchers from the University of Saskatchewan isolated UGM in a form bound to sugars and obtained its crystal structure. This information may be used to design drugs that inhibit the enzyme's activity and thus block the formation of bacterial cell walls. |
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Original Publication | CLS Science Highlights |
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J. Mol. Biol., Vol. 394(5), pp. 864-877. 2009
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