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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
45
Insights into Molecular Switch: Crystal Structure Analysis of Wild Type and Fast
Hydrolyzing Mutant of EhRabX3, a Tandem Ras Superfamily GTPase from Entamoeba
Histolytica
Mintu Chandra
1
, Vijay K. Srivastava
1
, Yumiko S. Nakano
2
, Tomoyoshi Nozaki
2
.Sunando
Datta
1
,
1
Indian Institute of Science Education and Research (IISER) Bhopal, Bhopal, Indiana,
India,
2
National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Shinjuku-ku, Tokyo,
Japan.
See abstract: 22-POS Board 22
Moving Forward New Medicines and New Targets in Malaria
Timothy Wells
.
Medicines for Malaria Venture, Geneva, Switzerland.
Drug discovery in malaria in the last decade has been built on two pillars and both of these have
shown success for some of the projects we have been collaborating on. First, structure-based
drug design has been used to optimize new molecules. Using the three dimensional structures of
dihydrofolate reductase new inhibitors have been designed to overcome resistance, and the
structure of dihydro-orotate dehydrogenase new classes of compound have been optimized
which are active against the parasite both in vitro, and in studies in patients and volunteers. On
the other hand, technological developments in phenotypic screening mean that almost 6 million
compounds have now been screened directly against the parasite. This has yielded several new
membrane bound targets, including the sodium channel PfATP4 and the lipid kinase PI4-kinase.
These represent high value targets for structural evaluation, and for structure based optimization,
especially if such models can be used to suggest new chemical scaffolds. The other output from
this process has been the availability of a collection of high value hits, called Malaria Box which
has been used as a test set by several groups to understand better the pharmacological impact of
these compounds on the parasite.