AI Article Synopsis
- Falcipain-2 and falcipain-3 are important enzymes in Plasmodium falciparum, the parasite responsible for malaria.
- Researchers determined the crystal structures of falcipain-2 and falcipain-3 with specific inhibitors, marking a first for understanding these enzymes at a molecular level.
- The study highlights how small changes in the enzyme's amino acids can significantly impact their shape, flexibility, and activity, which may explain differences in how these similar enzymes function.
Article Abstract
Falcipain-2 and falcipain-3 are critical hemoglobinases of Plasmodium falciparum, the most virulent human malaria parasite. We have determined the 2.9 A crystal structure of falcipain-2 in complex with the epoxysuccinate E64 and the 2.5 A crystal structure of falcipain-3 in complex with the aldehyde leupeptin. These complexes represent the first crystal structures of plasmodial cysteine proteases with small molecule inhibitors and the first reported crystal structure of falcipain-3. Our structural analyses indicate that the relative shape and flexibility of the S2 pocket are affected by a number of discrete amino acid substitutions. The cumulative effect of subtle differences, including those at "gatekeeper" positions, may explain the observed kinetic differences between these two closely related enzymes.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651692 | PMC |
| http://dx.doi.org/10.1021/jm8013663 | DOI Listing |
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