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Biochemical characterisation and novel classification of monofunctional S-adenosylmethionine decarboxylase of Plasmodium falciparum

Williams, Marni; Sprenger, Janina LU ; Human, Esmare; Al-Karadaghi, Salam; Persson, Lo LU ; Louw, Abraham I. and Birkholtz, Lyn-Marie (2011) In Molecular and Biochemical Parasitology 180(1). p.17-26
Abstract
Plasmodium falciparum like other organisms is dependent on polyamines for proliferation. Polyamine biosynthesis in these parasites is regulated by a unique bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). Only limited biochemical and structural information is available on the bifunctional enzyme due to the low levels and impurity of an instable recombinantly expressed protein from the native gene. Here we describe the high level expression of stable monofunctional PfAdoMetDC from a codon-harmonised construct, which permitted its biochemical characterisation indicating similar catalytic properties to AdoMetDCs of orthologous parasites. In the absence of structural data, far-UV CD showed that at least... (More)
Plasmodium falciparum like other organisms is dependent on polyamines for proliferation. Polyamine biosynthesis in these parasites is regulated by a unique bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). Only limited biochemical and structural information is available on the bifunctional enzyme due to the low levels and impurity of an instable recombinantly expressed protein from the native gene. Here we describe the high level expression of stable monofunctional PfAdoMetDC from a codon-harmonised construct, which permitted its biochemical characterisation indicating similar catalytic properties to AdoMetDCs of orthologous parasites. In the absence of structural data, far-UV CD showed that at least on secondary structure level, PfAdoMetDC corresponds well to that of the human protein. The kinetic properties of the monofunctional enzyme were also found to be different from that of PfAdoMetDC/ODC as mainly evidenced by an increased K-m. We deduced that complex formation of PfAdoMetDC and PfODC could enable coordinated modulation of the decarboxylase activities since there is a convergence of their k(cat) and lowering of their K-m. Such coordination results in the aligned production of decarboxylated AdoMet and putrescine for the subsequent synthesis of spermidine. Furthermore, based on the results obtained in this study we propose a new AdoMetDC subclass for plasmodial AdoMetDCs. (C) 2011 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Codon-harmonize, S-adenosylmethionine decarboxylase, Malaria, Oligomerization, Polyamines
in
Molecular and Biochemical Parasitology
volume
180
issue
1
pages
17 - 26
publisher
Elsevier
external identifiers
  • wos:000295545000003
  • scopus:80052778388
ISSN
1872-9428
DOI
10.1016/j.molbiopara.2011.07.004
language
English
LU publication?
yes
id
6f5480ca-16b9-4de1-9b60-22b454eb474e (old id 2212653)
date added to LUP
2011-12-01 08:33:40
date last changed
2017-01-01 03:59:02
@article{6f5480ca-16b9-4de1-9b60-22b454eb474e,
  abstract     = {Plasmodium falciparum like other organisms is dependent on polyamines for proliferation. Polyamine biosynthesis in these parasites is regulated by a unique bifunctional S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC). Only limited biochemical and structural information is available on the bifunctional enzyme due to the low levels and impurity of an instable recombinantly expressed protein from the native gene. Here we describe the high level expression of stable monofunctional PfAdoMetDC from a codon-harmonised construct, which permitted its biochemical characterisation indicating similar catalytic properties to AdoMetDCs of orthologous parasites. In the absence of structural data, far-UV CD showed that at least on secondary structure level, PfAdoMetDC corresponds well to that of the human protein. The kinetic properties of the monofunctional enzyme were also found to be different from that of PfAdoMetDC/ODC as mainly evidenced by an increased K-m. We deduced that complex formation of PfAdoMetDC and PfODC could enable coordinated modulation of the decarboxylase activities since there is a convergence of their k(cat) and lowering of their K-m. Such coordination results in the aligned production of decarboxylated AdoMet and putrescine for the subsequent synthesis of spermidine. Furthermore, based on the results obtained in this study we propose a new AdoMetDC subclass for plasmodial AdoMetDCs. (C) 2011 Elsevier B.V. All rights reserved.},
  author       = {Williams, Marni and Sprenger, Janina and Human, Esmare and Al-Karadaghi, Salam and Persson, Lo and Louw, Abraham I. and Birkholtz, Lyn-Marie},
  issn         = {1872-9428},
  keyword      = {Codon-harmonize,S-adenosylmethionine decarboxylase,Malaria,Oligomerization,Polyamines},
  language     = {eng},
  number       = {1},
  pages        = {17--26},
  publisher    = {Elsevier},
  series       = {Molecular and Biochemical Parasitology},
  title        = {Biochemical characterisation and novel classification of monofunctional S-adenosylmethionine decarboxylase of Plasmodium falciparum},
  url          = {http://dx.doi.org/10.1016/j.molbiopara.2011.07.004},
  volume       = {180},
  year         = {2011},
}