| Autor: |
Alla Gustchina, Pooja Kesari, Vandana Mishra, Mehdi Labaied, Huogen Xiao, Nikhil Pahelkar, Thomas E. Edwards, Anuradha Deshmukh, John H. Dupuis, Alexander Wlodawer, Prasenjit Bhaumik, Abhishek B. Suryawanshi, Ishan Rathore, Rickey Y. Yada, Donald D. Lorimer, Jan Abendroth |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Plasmodium falciparum plasmepsin X (PfPMX), 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 PfPMX zymogen containing a novel fold of its prosegment. A unique twisted loop from the prosegment and arginine 244 from the mature enzyme are involved in zymogen inactivation; such mechanism, not previously reported, might be common for apicomplexan proteases similar to PfPMX. The maturation of PfPMX zymogen occurs through cleavage of its prosegment at multiple sites. Our data provide thorough insights into the mode of binding of a substrate and a potent inhibitor 49c to PfPMX. We present molecular details of inactivation, maturation, and inhibition of PfPMX that should aid in the development of potent inhibitors against pepsin-like aspartic proteases from apicomplexan parasites. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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