Cysteine biosynthetic enzymes are the pieces of a metabolic energy pump.
Understanding the mechanisms of free energy transfer in metabolism is fundamental to understanding how the chemical forces that sustain the molecular organization of the cell are distributed. Recent studies of molecular motors (1-3) and ATP-driven proton transport (4-6) describe how chemical potential is transferred at the molecular level. These systems catalyze energy transfer through structural change and appear to be dedicated exclusively to their coupling tasks (7, 8). Here we report the discovery of a new class of energy-transfer system. It is a biosynthetic pump composed of cysteine biosynthesis enzymes, ATP sulfurylase and O-acetylserine sulfhydrylase, each with its own catalytic function and from whose interactions emerge new function: the hydrolysis of ATP. The hydrolysis is kinetically and energetically linked to the chemistry catalyzed by ATP sulfurylase, the first enzyme in the cysteine biosynthetic pathway, in such a way that each molecule of ATP hydrolyzed, each stroke of the pump, produces 1 equivalent of that enzyme's product. These findings integrate cysteine metabolism and broaden our understanding of the ways in which higher order allostery is used to effect free energy transfer.
Wei
Jiang
J
The Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461-1926, USA.
Tang
Qing-Xiu
QX
Varlamova
Olga
O
Roche
Camille
C
Lee
Reaching
R
Leyh
Thomas S
TS
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D003545:Cysteine / Q000096:biosynthesis*; D004734:Energy Metabolism; D004926:Escherichia coli / Q000201:enzymology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping
D011994:Recombinant Proteins; D006165:Guanylyl Imidodiphosphate; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D011770:Pyruvate Kinase; D003545:Cysteine