Four different enzymes share a similar catalytic mechanism which involves the
phosphorylation by ATP (or GTP) of a specific histidine residue in the active
site. These enzymes are:
ATP citrate-lyase (EC 2.3.3.8) [1], the primary enzyme responsible for the
synthesis of cytosolic acetyl-CoA in many tissues, catalyzes the formation
of acetyl-CoA and oxaloacetate from citrate and CoA with the concomitant
hydrolysis of ATP to ADP and phosphate. ATP-citrate lyase is a tetramer of
identical subunits.
Succinyl-CoA ligase (GDP-forming) (EC 6.2.1.4) [2] is a mitochondrial
enzyme that catalyzes the substrate level phosphorylation step of the
tricarboxylic acid cycle: the formation of succinyl-CoA from succinate with
a concomitant hydrolysis of GTP to GDP and phosphate. This enzyme is a
dimer composed of an α and a β subunits.
Succinyl-CoA ligase (ADP-forming) (EC 6.2.1.5) [3] is a bacterial enzyme
that during aerobic metabolism functions in the citric acid cycle, coupling
the hydrolysis of succinyl-CoA to the synthesis of ATP. It can also
function in the other direction for anabolic purposes. This enzyme is a
tetramer composed of two α and two β subunits.
Malate-CoA ligase (EC 6.2.1.9) (malyl-CoA synthetase) [4], is a bacterial
enzyme that forms malyl-CoA from malate and CoA with the concomitant
hydrolysis of ATP to ADP and phosphate. Malate-CoA ligase is composed of
two different subunits.
We developed three signature patterns for these enzymes, the first corresponds
to a glycine-rich conserved region, located in the second half of ATP citrate
lyase and in the α subunits of succinyl-CoA ligases and malate-CoA ligase.
The second pattern, which is located some 50 residues to the C-terminal of the
first one, includes the active site phosphorylated histidine residue. The last
pattern corresponds to a conserved region located in the first half of ATP
citrate lyase and in the β subunits of succinyl-CoA ligases and malate-CoA
ligase.
Genetics of the serine cycle in Methylobacterium extorquens AM1: identification, sequence, and mutation of three new genes involved in C1 assimilation, orf4, mtkA, and mtkB.
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