Back to "In addition, Mg-ATP inhibited GTP hydrol..."
Strong Support
mechanistic
Analysis v2
History

In human tissue transglutaminase, magnesium-bound ATP strongly blocks GTP breakdown at low concentrations, while magnesium-bound GTP only weakly blocks ATP breakdown even at high concentrations,...

33
Pro
0
Against

Mechanism

Synthesis from 1 study

How it works

The enzyme has two different spots for energy molecules: one for ATP and one for GTP. ATP locks into its spot tightly and shuts down the enzyme’s ability to break down GTP, but GTP can’t do the same to ATP — even when there’s a lot of it. This one-way control lets ATP act like a master switch for...

Most probable mechanism

In Simple Terms

When magnesium-bound ATP is present, it binds tightly to a specific spot on the enzyme and blocks it from breaking down magnesium-bound GTP, but the reverse doesn’t happen — even high levels of magnesium-bound GTP barely slow down ATP breakdown. This happens because the enzyme has two different spots for these molecules, and ATP fits much better and changes the enzyme’s shape in a way that strongly interferes with GTP processing.

Causal chain
1

Magnesium-bound ATP binds with high affinity to a distinct nucleotide-binding site on tissue transglutaminase

Verified by multiple studies
which leads to
2

Binding of magnesium-bound ATP induces a conformational change in the enzyme that reduces the catalytic efficiency of the GTP hydrolysis site

Verified by multiple studies
which leads to
3

This conformational change competitively or allosterically suppresses the hydrolysis of magnesium-bound GTP without significantly affecting ATP hydrolysis

Verified by multiple studies
which leads to
4

Magnesium-bound GTP binds to a separate site with lower affinity and inhibits transglutaminase activity through a different conformational change, but has minimal effect on ATP hydrolysis

Verified by multiple studies

Evidence from Studies

Supporting (1)

33

Community contributions welcome

33

Regulation of Human Tissue Transglutaminase Function by Magnesium-Nucleotide Complexes

Case-Control Study
In Vitro
1998 Jan 16

Contradicting (0)

0

Community contributions welcome

No contradicting evidence found

Gold Standard Evidence Needed

According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.

Sign up to see full verdict

Source Study

Regulation of Human Tissue Transglutaminase Function by Magnesium-Nucleotide Complexes

Score: 33
DOI: 10.1074/jbc.273.3.1776

Similar Assertions

The enzyme transglutaminase in human tissues has separate molecular pockets that bind Mg-GTP and Mg-ATP, allowing it to respond differently to each molecule based on their chemical structure.

33
0
87%

Human tissue transglutaminase enzyme uses two magnesium-bound nucleotides, Mg-ATP and Mg-GTP, as substrates for hydrolysis, and Mg-ATP binds more tightly to the enzyme than Mg-GTP, suggesting differences in how the enzyme interacts with each molecule.

33
0
85%

When Mg-GTP binds to the enzyme tissue transglutaminase, it prevents the enzyme from being broken down by trypsin; Mg-ATP does not have this effect, suggesting that Mg-GTP changes the enzyme's shape in a way that makes it more stable.

33
0
85%

Magnesium-bound guanine nucleotides (Mg-GTP, Mg-GDP, Mg-GMP) reduce the activity of human tissue transglutaminase at specific concentrations, while magnesium-bound adenine nucleotides do not, indicating that the enzyme is selectively regulated by guanine-based molecules.

33
0
83%

In human tissue transglutaminase, the rates at which the enzyme breaks down GTP and ATP change in a coordinated way when the protein is shortened at its end, indicating that both molecules are processed by the same active site.

28
0
81%