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Journal of Tropical Medicine
Volume 2012 (2012), Article ID 646534, 15 pages
http://dx.doi.org/10.1155/2012/646534
Review Article

On Programmed Cell Death in Plasmodium falciparum: Status Quo

1Plasmodium Molecular Research Unit, Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg 2193, South Africa
2Evolutionary Medicine Unit, Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand and National Health Laboratory Service, Johannesburg 2193, South Africa
3Department of Molecular Medicine and Haematology, Wits Medical School, Room 7Q11, 7 York Road, Parktown, Johannesburg 2193, South Africa

Received 31 December 2010; Accepted 16 September 2011

Academic Editor: Wilbur Milhous

Copyright © 2012 Dewaldt Engelbrecht et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplementary Material

In a recent study, six key proteins or domains were selected based on their involvement in the four main stages of the p53-dependent pathway: induction (ATM), initiation (p53), regulation (MDM2, CR6 and IAP) and execution (peptidase C14). Hidden Markov model (HMM) libraries were constructed (supplementary file which is available online at doi:10.1155/2012/646534, [66]). A detailed analysis of the four Plasmodium genomes was performed using these HMM libraries, as well as an array of computational approaches including standard homology methods, phylogenetics, structural models and a novel evolutionary rate-based alignment algorithm FIRE (Functional Inference using the Rates of Evolution), which was developed to identify homologous and analogous genes in organisms with unusual genomes, such as P. falciparum, and hence low sequence similarity [81]. Hits are listed in the table below with E-values in parentheses. Fifteen hits with negative E-values were retrieved from the HMM library for p53 DNA binding domains (DBD) and two of these are included in the table. These encode proteins containing predicted p53 DBD-like structural folds (antiparallel beta sheets with greek key topology) according to PlasmoDB v5.5 and positive FIRE scores. The FIRE algorithm predicts the function of a domain based upon similar evolutionary rates and produced scores of 0.71 and 0.68 for PFE1120w and PFE0325, respectively (FIRE scores greater than 0.6 are suggestive of similar functions).

  1. Supplementary Material