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Inhibition and Allosteric Regulation of Monomeric

Phosphoenolpyruvate Carboxykinase by 3-Mercaptopicolinic
Acid
Mark D. Balan, Matthew J. Mcleod, William R. Lotosky, Mark Ghaly, and Todd Holyoak

Metabolic pathway that PEPCK is involved in:

-O

OO

O-

P
O

phosphoenolpyruvate

-O

OO
oxaloacetate

PEPCK

Glycolysis role in metabolism:

Break down glucose to create ATP and pyruvate.
Pyruvate is then used in the citric acid cycle to
produce more ATP.

Gluconeogenesis role in metabolism:
Make glucose from precursors in cell, esp.
pyruvate.

Hypoglycemic agent = something that leads to low levels of glucose (low blood sugar)

P-loop motif = Many phosphate-binding proteins have a phosphate-binding loop (P-loop).
The consensus sequence for this structure is GXXXXGKT/S.

Skip the Experimental section unless you are interested in how to do crystallography (we will not
discuss it in class).

Reaction mechanism of PEPCK:









from: "Structural Insights into the Mechanism of Phosphoenolpyruvate Carboxykinase Catalysis"
Carlson and Holyoak, J Biol Chem. 2009 Oct 2; 284(40): 2703727041.


In the section of the Results and Discussion enitled Crystallography, you don't need to pay attention
to the details of the structure determination. When they talk about disordered loops they mean that
some loops in the protein are flexible and so are missing from the x-ray structure because it is a
"snapshot" of the protein structure. Anything in motion is not clearly visible.