NDLI: Flap flexibility amongst plasmepsins I, II, III, IV, and V: Sequence, structural, and molecular dynamics analyses.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	McGillewie, Lara Soliman, Mahmoud E.
Description	Country affiliation: South Africa Author Affiliation: McGillewie L ( Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.); Soliman ME ( Molecular Modelling & Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4001, South Africa.)
Abstract	Herein, for the first time, we comparatively report the opening and closing of apo plasmepsin I - V. Plasmepsins belong the aspartic protease family of enzymes, and are expressed during the various stages of the P. falciparum lifecycle, the species responsible for the most lethal and virulent malaria to infect humans. Plasmepsin I, II, IV and HAP degrade hemoglobin from infected red blood cells, whereas plasmepsin V transport proteins crucial to the survival of the malaria parasite across the endoplasmic reticulum. Flap-structures covering the active site of aspartic proteases (such as HIV protease) are crucial to the conformational flexibility and dynamics of the protein, and ultimately control the binding landscape. The flap-structure in plasmepsins is made up of a flip tip in the N-terminal lying perpendicular to the active site, adjacent to the flexible loop region in the C-terminal. Using molecular dynamics, we propose three parameters to better describe the opening and closing of the flap-structure in apo plasmepsins. Namely, the distance, d1, between the flap tip and the flexible region; the dihedral angle, Ï, to account for the twisting motion; and the TriC angle, Î¸1. Simulations have shown that as the flap-structure twists, the flap and flexible region move apart opening the active site, or move toward each other closing the active site. The data from our study indicate that of all the plasmepsins investigated in the present study, Plm IV and V display the highest conformational flexibility and are more dynamic structures versus Plm I, II, and HAP.
File Format	HTM / HTML
ISSN	08873585
Issue Number	9
Volume Number	83
e-ISSN	10970134
Journal	Proteins: Structure, Function, and Bioinformatics
Language	English
Publisher	Wiley-Liss
Publisher Date	2015-09-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Protein Structure, Tertiary Amino Acid Sequence Research Support, Non-u.s. Gov't Catalytic Domain Plasmodium Falciparum Protein Structure, Secondary Discipline Biochemistry Protozoan Proteins Metabolism Molecular Dynamics Simulation Journal Article Chemistry Aspartic Acid Endopeptidases Protein Conformation Genetics Kinetics
Content Type	Text
Resource Type	Article
Subject Domain (in MeSH)	Eukaryota Enzymes and Coenzymes Amino Acids, Peptides, and Proteins Investigative Techniques Physical Phenomena Chemical Phenomena
Subject	Molecular Biology Biochemistry Structural Biology

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