Characterisation of a putative glutamate 5-kinase from Leishmania donovani.

The FEBS Journal
Natasha SienkiewiczAlan H Fairlamb

Abstract

Previous metabolic studies have demonstrated that leishmania parasites are able to synthesise proline from glutamic acid and threonine from aspartic acid. The first committed step in both biosynthetic pathways involves an amino acid kinase, either a glutamate 5-kinase (G5K; EC2.7.2.11) or an aspartokinase (EC2.7.2.4). Bioinformatic analysis of multiple leishmania genomes identifies a single amino acid-kinase gene (LdBPK 262740.1) variously annotated as either a putative glutamate or aspartate kinase. To establish the catalytic function of this Leishmania donovani gene product, we have determined the physical and kinetic properties of the recombinant enzyme purified from Escherichia coli. The findings indicate that the enzyme is a bona fide G5K with no activity as an aspartokinase. Tetrameric G5K displays kinetic behaviour similar to its bacterial orthologues and is allosterically regulated by proline, the end product of the pathway. The structure-activity relationships of proline analogues as inhibitors are broadly similar to the bacterial enzyme. However, unlike G5K from E. coli, leishmania G5K lacks a C-terminal PUA (pseudouridine synthase and archaeosine transglycosylase) domain and does not undergo higher oligomerisation in...Continue Reading

References

Jan 1, 1976·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·D Sylvester, S M Krassner
Sep 1, 1992·The Journal of protozoology·B H Ter Kuile, F R Opperdoes
Jul 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P I FieldsF Heffron
Nov 1, 1972·The Journal of protozoology·S M Krassner, B Flory
Nov 1, 1972·The Journal of protozoology·D A Evans, R C Brown
Jan 1, 1973·Transactions of the Royal Society of Tropical Medicine and Hygiene·W C Ford, I B Bowman
Mar 1, 1965·Journal of Theoretical Biology·E Zuckerkandl, L Pauling
Sep 1, 1994·Molecular and Biochemical Parasitology·S DeyM Ouellette
Jul 14, 1998·Antimicrobial Agents and Chemotherapy·A Haimeur, M Ouellette
Aug 10, 2000·Nature Medicine·B Reina-San-MartínP Minoprio
Sep 22, 2001·International Journal for Parasitology·R J Burchmore, M P Barrett
Oct 11, 2003·Molecular and Biochemical Parasitology·Sophie GoyardStephen M Beverley
Jul 15, 2004·The Journal of Biological Chemistry·Susan WyllieAlan H Fairlamb
Jan 14, 2005·The Journal of Biological Chemistry·Susanne W H van WeeldenAloysius G M Tielens
Jan 19, 2006·Clinical Microbiology Reviews·Simon L CroftAlan H Fairlamb
Mar 30, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thomas NadererMalcolm J McConville
Feb 27, 2007·Trends in Parasitology·Fred R Opperdoes, Graham H Coombs
Sep 22, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Doron RosenzweigDan Zilberstein
Apr 3, 2008·The Journal of Clinical Investigation·Ken StuartRick Tarleton
Mar 25, 2009·Antimicrobial Agents and Chemotherapy·Philippe LeprohonMarc Ouellette
Mar 26, 2009·Journal of Medicinal Chemistry·Paola BaioccoAndrea Ilari
Apr 30, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Heather KunUNKNOWN Chagas Disease in Transplant Recipients Investigation Team
Oct 16, 2009·The Journal of Biological Chemistry·Leah S TorrieJulie A Frearson
Jun 15, 2010·Extremophiles : Life Under Extreme Conditions·Isabel Pérez-Arellano, Javier Cervera
Jun 16, 2010·Molecular Microbiology·Natasha SienkiewiczAlan H Fairlamb
Jun 18, 2010·Molecular and Biochemical Parasitology·Susan WyllieMitali Chatterjee
Jul 27, 2010·Ecotoxicology and Environmental Safety·Milan PavlíkPavel Tlustos
Oct 26, 2010·Journal of Molecular Biology·Isabel Pérez-ArellanoJavier Cervera
Jul 9, 2011·Molecular and Biochemical Parasitology·Neha BiyaniRentala Madhubala
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Frederic BringaudDan Zilberstein
Mar 1, 2012·Parasitology·Polina TsigankovDan Zilberstein

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Citations

Dec 5, 2019·Metallomics : Integrated Biometal Science·Johana Vásquez-ProcopioFanis Missirlis
Aug 5, 2020·Journal of Industrial Microbiology & Biotechnology·Naoyuki MurakamiHiroshi Takagi

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Methods Mentioned

BETA
PCR
size exclusion chromatography
transgenic
phosphotransferase
transfection
environmental stress

Software Mentioned

GraFit
mega7

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