Allostery Activators

Allosteric enzymes show various activation and inhibition effects which are competitive in nature and related to conformational changes in the structure of the enzyme. Such allosteric enzymes are often crucial enzymes in metabolic pathways and exert control over the whole sequence of reactions. The name allostery refers to the fact that inhibition of the enzyme is by substances that are not similar in shape to the substrate. 

The ability of proteins to exist in different conformations is termed allostery (see 2.2). Allosteric enzymes can assume various conformations which differ in catalytic activity and/or substrate binding capacity. 

The symmetry model (fig. 2.4) of allostery can describe the cooperative binding of substrate to enzyme (homotropic effect), as well as the influence of effector molecules on the activity of enzymes (heterotropic effect). 

There are two major isoenzymes of ACC in mammalian tissues, ACCl and ACC2. ACCl is strictly cytosolic and is enriched in liver, adipose tissue and lactating mammary tissue. ACC2 is expressed in heart and skeletal muscle, and liver. Both isoenzymes are allosteri-cally activated by citrate and inhibited by palmitoyl-CoA and other short- and long-chain fatty acyl-CoAs. Citrate triggers the polymerisation of ACCl, which leads to significant increases in its activity. 

Di Cera E, Page MJ, Bah A, Bush-Pelc LA, Garvey LC. Thrombin allostery. Phys. Chem. Chemical Phys. 2007 9 1291-1306. Li L, Uversky VN, Dunker AK, Meroueh SO. Computational investigation of allostery in the catabolite activator protein. J. Am. Chem. Soc. 2007 129 15668-15676. 

The first coordination shell of Fe in Fib is identical to that of Mb, but there are other major differences that influence the spectroelectrochemical/Nernst plot profile of Hb and make it distinct from that of Mb. Hb is a tetrameric protein with four heme-containing subunits (a2p2), each of which is redox-active. Differences between Mb and Hb include amino-acid sequence, which results in different redox potentials for the a and (3 chains, plus subunit-subunit interactions that lead to allostery in Hb. This allosteric interaction leads to cooperative electron transfer that gives rise to a non-Nernstian redox profile that requires special consideration for data analysis and interpretation of results. ... 

Many proteins are regulated by molecules which bind somewhere other than at the active site and either inerease or decrease protein activity. These allosteric ejfectors are often quite specific and may have either a positive or negative effect upon protein activity. C ass cdX feedback inhibition cycles in metabolism generally involve heterotropic allostery, in which a molecule produced near the end of a metabolic pathway acts as an allosteric effector to regulate a protein active earlier in the same pathway. Because of the need for very precise control of the energy charge of the cell, ATP and ADP serve as allosteric effectors for several of the proteins of glucose metabolism. Protons and ions act as allosteric effectors in many... 

Advances in X-ray crystallography and nuclear magnetic resonance spectroscopy have facilitated the solution of a range of other allosteric proteins. These structures have contributed significantly to our understanding of the nature of allostery and the complex atomic level changes that accompany transitions from active/high affinity conformations to in-... 

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