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Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.” 
Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.”
Walter and Eliza Hall Institute
In uncovering how an antibiotic fights malaria, investigators may have enabled the development of safer and more effective antimalarial drugs.
The group has determined how the antibiotic emetine blocks the molecular machinery that produces the proteins required for malaria parasite survival.
Although emetine is known to be effective against malaria, the drug is not used for this purpose because it confers significant side effects.
By gaining new insight into how emetine works, the investigators have forged the way ahead for designing drugs that can provide the efficacy of emetine without the adverse effects.
Wilson Wong, PhD, of the Walter and Eliza Hall Institute in Victoria, Australia, and his colleagues described this research in eLife.
For this work, the team used Cryo-EM, a technique that allows researchers to visualize the structure of protein complexes from cellular material without having to crystallize them. This method revealed how emetine binds to the ribosome of the malaria parasite Plasmodium falciparum.
“The ribosome is responsible for constructing all proteins inside the cell, based on the DNA ‘blueprint,’” Dr Wong said. “Antibiotics such as emetine kill the malaria parasite by binding to its ribosome and preventing the parasite from building the proteins it needs to produce energy, grow, reproduce, and evade the immune system.”
The investigators discovered that emetine interacts with the E-site of the ribosomal small subunit and shares a similar binding site with the antibiotic pactamycin. And emetine delivers its antimalaria effect by blocking mRNA/tRNA translocation.
“Our structure is an exciting discovery, as it gives a clear path forward in developing new drugs to tackle this deadly disease,” Dr Wong said. “We have found features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features in order to specifically target the production of proteins within the malaria parasite.”
“We are now working with our colleagues from the institute’s ACRF Chemical Biology division to develop new molecules based on emetine and pactamycin. Knowing exactly how these antibiotics work will enable development of new antimalarial drugs that replicate the active component of these antibiotics, while changing the parts that make it toxic to patients.”