On the location of the aminopeptidase N homolog Pf A-M1 in Plasmodium falciparum
Year: 2009
Type: letter
Abstract: The malaria parasite Plasmodium falciparum contains a single aminopeptidase N homolog (termed PfA-M1; ref. 1) that has been proposed to play an important role in the parasite's catabolism of host red blood cell hemoglobin in its food vacuole (2). In their report on PfA-M1, McGowan et al. (3) claim to provide evidence that this enzyme is located in the parasite cytosol. However, the arguments that they present in support of a cytosolic location of PfA-M1 are flawed. First, the authors localize in P. falciparum a form of PfA-M1 that lacks the amino-terminal 194 amino acids (Fig. 1B in ref. 3). The physiological relevance of this experiment is not clear. This truncated form of PfA-M1 is missing the N-terminal signal peptide (or transmembrane sequence) that is almost certainly an important determinant of the protein's ultimate cellular destination. The other piece of evidence presented in support of a cytosolic location is the relative PfA-M1 activity at a single concentration of a fluorogenic substrate as a function of pH (Fig. 1D in ref. 3). An optimum pH of 7.0 for PfA-M1 activity is used to argue consistency with a cytosolic role. Such a conclusion is unwarranted. Experiments such as those in Fig. 1D of ref. 3 lend little insight into the true pH–activity relationships of enzymes as they do not report on the enzyme's intrinsic catalytic properties (Km and kcat). The effect of pH on PfA-M1 catalysis of globin peptide hydrolysis is likely to be complex because it will vary considerably depending on the chemical properties of each peptide substrate.
Author: Michael Klemba
Institution: Virginia Tech
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2010842391