NEGATIVE COOPERATIVITY IN REGULATORY ENZYMES

Structural basis of negative cooperativity in transthyretin.

A comparison of the AC and BD binding sites of transthyretin (TTR) was made in terms of the interatomic distances between the Ca atoms of equivalent amino acids, measured across the tetramer channel in each binding site. The comparison of the channel diameter for apo TTR from different sources revealed that in the unliganded transthyretin tetramers the distances between the A, D and H beta-stra...

Cooperativity in biological systems

Living organisms can sense and respond to external and internal stimuli. Response isdemonstrated in many forms including modulation of gene expression profiles, motility,secretion, cell death, etc. Nevertheless, all forms share a basic property: they depend on sensingsmall changes in the concentration of an effector molecule or subtle conformational changes ina protein and invoking the appropri...

Allosteric Regulatory Enzymes

The Nature of Negative Cooperativity in Alkaline Phosphatase

The nature of strong negative cooperativity displayed by alkaline phosphatase from Escherichia coli was investigated by alternative substrate and product inhibition studies, and by catalytic rate constant (kcat) measurements. To see whether the idled subunit in this dimeric enzyme plays a mechanistic role in the overall catalysis, the flip-flop model proposed by Lazdunski et al. ((1971) Eur. J....

Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness

Negative autoregulation is universally found across organisms. In the bacterium Escherichia coli, transcription factors often repress their own expression to form a negative feedback network motif that enables robustness to changes in biochemical parameters. Here we present a simple phenomenological model of a negative feedback transcription factor repressing both itself and another target gene...