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A unique insertion of low complexity amino acid sequence underlies protein-protein interaction in human malaria parasite orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase.

AbstractOBJECTIVE:
To investigate the multienzyme complex formation of human malaria parasite Plasmodium falciparum (P. falciparum) orotate phosphoribosyltransferase (OPRT) and orotidine 5'-monophosphate decarboxylase (OMPDC), the fifth and sixth enzyme of the de novo pyrimidine biosynthetic pathway. Previously, we have clearly established that the two enzymes in the malaria parasite exist physically as a heterotetrameric (OPRT)2(OMPDC)2 complex containing two subunits each of OPRT and OMPDC, and that the complex have catalytic kinetic advantages over the monofunctional enzyme.
METHODS:
Both enzymes were cloned and expressed as recombinant proteins. The protein-protein interaction in the enzyme complex was identified using bifunctional chemical cross-linker, liquid chromatography-mass spectrometric analysis and homology modeling.
RESULTS:
The unique insertions of low complexity region at the α 2 and α 5 helices of the parasite OMPDC, characterized by single amino acid repeat sequence which was not found in homologous proteins from other organisms, was located on the OPRT-OMPDC interface. The structural models for the protein-protein interaction of the heterotetrameric (OPRT)2(OMPDC)2 multienzyme complex were proposed.
CONCLUSIONS:
Based on the proteomic data and structural modeling, it is surmised that the human malaria parasite low complexity region is responsible for the OPRT-OMPDC interaction. The structural complex of the parasite enzymes, thus, represents an efficient functional kinetic advantage, which in line with co-localization principles of evolutional origin, and allosteric control in protein-protein-interactions.
AuthorsWaranya Imprasittichail, Sittiruk Roytrakul, Sudaratana R Krungkrai, Jerapan Krungkrail
JournalAsian Pacific journal of tropical medicine (Asian Pac J Trop Med) Vol. 7 Issue 3 Pg. 184-92 (Mar 2014) ISSN: 2352-4146 [Electronic] India
PMID24507637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Protozoan Proteins
  • Recombinant Proteins
  • Orotate Phosphoribosyltransferase
  • Orotidine-5'-Phosphate Decarboxylase
Topics
  • Amino Acid Sequence
  • Humans
  • Malaria, Falciparum (parasitology)
  • Models, Molecular
  • Molecular Sequence Data
  • Orotate Phosphoribosyltransferase (chemistry, genetics, metabolism)
  • Orotidine-5'-Phosphate Decarboxylase (chemistry, genetics, metabolism)
  • Plasmodium falciparum (enzymology, genetics)
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protozoan Proteins (chemistry, genetics, metabolism)
  • Recombinant Proteins (chemistry, genetics, metabolism)
  • Sequence Alignment

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