Phosphomevalonate kinase: functional investigation of the recombinant human enzyme

Biochemistry
Timothy J Herdendorf, Henry M Miziorko

Abstract

Phosphomevalonate kinase (PMK) catalyzes a key step in isoprenoid/sterol biosynthesis, converting mevalonate 5-phosphate and ATP to mevalonate 5-diphosphate and ADP. To expedite functional and structural study of this enzyme, an expression plasmid encoding His-tagged human PMK has been constructed and recombinant enzyme isolated in an active, stable form. PMK catalyzes a reversible reaction; kinetic constants of human PMK have been determined for both forward (formation of mevalonate 5-diphosphate) and reverse (formation of mevalonate 5-phosphate) reactions. Animal and invertebrate PMKs are not orthologous to plant, fungal, or bacterial PMKs, limiting the information available from sequence alignment analysis. A homology model for the structure of human PMK has been generated. The model conforms to a nucleoside monophosphate kinase family fold. This result, together with sequence comparisons of animal and invertebrate PMKs, suggests an N-terminal basic residue rich sequence as a possible "Walker A" ATP binding motif. The functions of four basic (K17, R18, K19, K22) residues and one acidic (D23) residue in the conserved sequence have been tested by mutagenesis and characterization of isolated mutant proteins. Substrate K(m) valu...Continue Reading

References

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Citations

Oct 2, 2007·Biochemistry·Timothy J Herdendorf, Henry M Miziorko
Jul 24, 2010·Molecular Biology and Evolution·Jonathan Lombard, David Moreira
Jan 11, 2013·Archaea : an International Microbiological Journal·Jonathan LombardDavid Moreira
Mar 19, 2013·Parasites & Vectors·Natalia González-CaballeroReginaldo P Brazil
Jan 30, 2014·PloS One·David E Garcia, Jay D Keasling
Sep 12, 2013·International Journal of Molecular Sciences·Yuan YuanLuqi Huang
Aug 20, 2014·Biochemistry·Timothy J Herdendorf, Scott W Nelson
Jan 18, 2011·Biochimica Et Biophysica Acta·Linda HennemanHans R Waterham
May 13, 2009·Journal of Biotechnology·Xiusheng ChuDing Li
Oct 30, 2007·Biochimica Et Biophysica Acta·Xiusheng ChuDing Li
Jul 12, 2008·Proteins·Qing ChangDong-Cai Liang
Feb 20, 2010·Molecular Nutrition & Food Research·Jean-Marc ZinggAngelo Azzi
Sep 16, 2006·Archives of Biochemistry and Biophysics·Jaime EyzaguirreEmilio Cardemil
Apr 16, 2013·Biochemical Pharmacology·Alexander MazeinPeter Ghazal
Nov 14, 2012·Biochemical and Biophysical Research Communications·Pornthip BoonsriDaniel S Sem
Oct 12, 2010·Archives of Biochemistry and Biophysics·Henry M Miziorko
Sep 8, 2016·Biochemistry·Nuno M F S A CerqueiraP A Fernandes

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