Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action.
Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum.
Dissection of the pH dependence of inhibitor binding energetics for an aspartic protease: direct measurement of the protonation states of the catalytic aspartic acid residues.
Structural analysis of plasmepsin II. A comparison with human aspartic proteases.
Evaluation of a structure-based statine cyclic diamino amide encoded combinatorial library against plasmepsin II and cathepsin D.
Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library.
Potent, low-molecular-weight non-peptide inhibitors of malarial aspartyl protease plasmepsin II.
X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF ZYMOGEN.
Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.
Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors.
Active site specificity of plasmepsin II.
New class of small nonpeptidyl compounds blocks Plasmodium falciparum development in vitro by inhibiting plasmepsins.
Active site contribution to specificity of the aspartic proteases plasmepsins I and II.
New antiinfective and human 5-HT2 receptor binding natural and semisynthetic compounds from the Jamaican sponge Smenospongia aurea.
Spermine alkaloids from Albizia adinocephala with activity against Plasmodium falciparum plasmepsin II.
Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 A in complex with the inhibitors rs367 and rs370.
Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum.
This enzyme belongs to the peptidase family-A1. According to the literature [3] & [16], this enzyme has got a catalytic dyad, composed of two aspartate residues. One is ionized and the other is protonated around the physiological pH. The paper [1] proposed a catalytic mechanism for its homologous enzyme. Accoriding to the proposed mechanism, the sidechains of both the aspartic acid residues are hydrogen-bonded to the catalytic water. The sidechain of the ionized aspartate (possibly corresponding to Asp214) might act as a general base, which can abstract a proton from the water, which in turn would make a nucleophilic attack on the carbonyl carbon of the peptide bond. Meanwhile, the protonated sidechain of the other aspartate (corresponding to Asp34) may stabilize the negative charge on the carbonyl oxygen of the scissile bond during the transition state. At the next stage, the sidechain of the aspartate that had accepted a proton from water could protonate the leaving nitrogen atom, as a general acid, during the cleavage of the peptide bond.