The protonation state of the catalytic aspartates in plasmepsin II

TitleThe protonation state of the catalytic aspartates in plasmepsin II
Publication TypeJournal Article
Year of Publication2007
AuthorsFriedman R., Caflisch A.
JournalFEBS Letters
Date Published2007 Aug 21
Type of ArticleResearch Article
KeywordsAnimals, Aspartic Acid, Aspartic Acid Endopeptidases, Catalytic Domain, Computer Simulation, Hydrogen Bonding, Models, Molecular, Plasmodium, Protons, Protozoan Proteins, Water

Assigning the correct protonation state to the catalytic residues is essential for a realistic modelling of an enzyme's active site. Plasmepsins are pharmaceutically relevant aspartic proteases involved in haemoglobin degradation by Plasmodium spp. In aspartic proteases, one of the two catalytic aspartates is protonated, while the other is negatively charged. Here, multiple explicit-water molecular dynamics simulations of plasmepsin II, uncomplexed and with a hydroxypropylamine peptidomimetic inhibitor, indicate that protonation of Asp214 favours a stable active site structure. Moreover, the protonation state of the catalytic aspartate has a strong influence on a linear chain of hydrogen bonds with the adjacent side chains.



Alternate JournalFEBS Lett.
PubMed ID17689534
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