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The evolution of catalytic residues and enzyme mechanism within the bacterial nucleoside phosphorylase superfamily 1

Konrad, Anke; Piskur, Jure LU and Liberles, David A. (2012) In Gene 510(2). p.154-161
Abstract
Nucleoside phosphorylases are essential for the salvage and catabolism of nucleotides in bacteria and other organisms, and members of this enzyme superfamily have been of interest for the development of antimicrobial and cancer therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of different enzymes which share a general superfold and catalytic mechanism, while they differ in the nature of the nucleophiles used and in the nature of characteristic active site residues. Recently, one subfamily, the uridine phosphorylases, has been subdivided into two types which differ with respect to the mechanism of transition state stabilization, as dictated by differences in critical amino acid residues. Little is known about the... (More)
Nucleoside phosphorylases are essential for the salvage and catabolism of nucleotides in bacteria and other organisms, and members of this enzyme superfamily have been of interest for the development of antimicrobial and cancer therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of different enzymes which share a general superfold and catalytic mechanism, while they differ in the nature of the nucleophiles used and in the nature of characteristic active site residues. Recently, one subfamily, the uridine phosphorylases, has been subdivided into two types which differ with respect to the mechanism of transition state stabilization, as dictated by differences in critical amino acid residues. Little is known about the phylogenetic distribution and relationship of the two different types, as well as the relationship to other NP-1 superfamily members. Here comparative genomic analysis illustrates that UP-Is and UP-2s fall into monophyletic groups and are biased with respect to species representation. UP-1 evolved in Gram negative bacteria, while Gram positive species tend to predominantly contain UP-2. PNP (a sister clade to all UPs) contains both Gram positive and Gram negative species. The findings imply that the nucleoside phosphorylase superfamily I evolved through a series of three important duplications, leading to the separate, monophyletic enzyme families, coupled to individual lateral transfer events. Extensive horizontal transfer explains the occurrence of unexpected uridine phosphorylases in some genomes. This study provides a basis for understanding the evolution of uridine and purine nucleoside phosphorylases with respect to DNA/RNA metabolism and with potential utility in the design of antimicrobial and anti-tumor drugs. (C) 2012 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Uridine phosphorylase, Purine nucleoside phosphorylase, Catalytic, residue evolution, Salvage pathway, Phylogeny, Bacterial Gene family
in
Gene
volume
510
issue
2
pages
154 - 161
publisher
Elsevier
external identifiers
  • wos:000311069300010
  • scopus:84867331508
ISSN
1879-0038
DOI
10.1016/j.gene.2012.08.046
language
English
LU publication?
yes
id
8d19502b-9bb2-422a-8c84-30c7d7e0e3ca (old id 3243074)
date added to LUP
2012-12-19 06:10:51
date last changed
2017-01-01 06:21:59
@article{8d19502b-9bb2-422a-8c84-30c7d7e0e3ca,
  abstract     = {Nucleoside phosphorylases are essential for the salvage and catabolism of nucleotides in bacteria and other organisms, and members of this enzyme superfamily have been of interest for the development of antimicrobial and cancer therapies. The nucleotide phosphorylase superfamily 1 encompasses a number of different enzymes which share a general superfold and catalytic mechanism, while they differ in the nature of the nucleophiles used and in the nature of characteristic active site residues. Recently, one subfamily, the uridine phosphorylases, has been subdivided into two types which differ with respect to the mechanism of transition state stabilization, as dictated by differences in critical amino acid residues. Little is known about the phylogenetic distribution and relationship of the two different types, as well as the relationship to other NP-1 superfamily members. Here comparative genomic analysis illustrates that UP-Is and UP-2s fall into monophyletic groups and are biased with respect to species representation. UP-1 evolved in Gram negative bacteria, while Gram positive species tend to predominantly contain UP-2. PNP (a sister clade to all UPs) contains both Gram positive and Gram negative species. The findings imply that the nucleoside phosphorylase superfamily I evolved through a series of three important duplications, leading to the separate, monophyletic enzyme families, coupled to individual lateral transfer events. Extensive horizontal transfer explains the occurrence of unexpected uridine phosphorylases in some genomes. This study provides a basis for understanding the evolution of uridine and purine nucleoside phosphorylases with respect to DNA/RNA metabolism and with potential utility in the design of antimicrobial and anti-tumor drugs. (C) 2012 Elsevier B.V. All rights reserved.},
  author       = {Konrad, Anke and Piskur, Jure and Liberles, David A.},
  issn         = {1879-0038},
  keyword      = {Uridine phosphorylase,Purine nucleoside phosphorylase,Catalytic,residue evolution,Salvage pathway,Phylogeny,Bacterial Gene family},
  language     = {eng},
  number       = {2},
  pages        = {154--161},
  publisher    = {Elsevier},
  series       = {Gene},
  title        = {The evolution of catalytic residues and enzyme mechanism within the bacterial nucleoside phosphorylase superfamily 1},
  url          = {http://dx.doi.org/10.1016/j.gene.2012.08.046},
  volume       = {510},
  year         = {2012},
}