+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Enzyme substrate and inhibitor interactions

Enzyme substrate and inhibitor interactions

Philosophical Transactions of the Royal Society of London. Series B Biological Sciences 272(915): 87-97

An enzyme is designed to bind most tightly to a substrate when it is in the transition state of the reaction which the enzyme catalyses. The consequent reduction of the activation energy of the reaction constitutes the catalytic mechanism. The energetic contributions of different features of the interaction can only be crudely assessed, but they are dominated by entropically driven effects. The binding site of trypsin orients the substrate so that the reacting groups are correctly placed for reaction to occur. Apart from two side chains which take part in chemical steps of the reaction, the enzyme behaves almost as a rigid body. The full binding interactions are only developed when the substrate is in an intermediate stage of the reaction. The tightly bound complexes of trypsin with protein trypsin inhibitors have proved amenable to structural analysis. Enzyme inhibitor interactions, which account for almost 80 kJ mol-1 of interaction energy, are known fairly accurately. The similarity of the two known trypsin inhibitor structures, close to the primary binding site, indicates a high specificity, even for this simple interaction. In cases where no large conformational changes occur the specificity of an enzyme should be predictable from accurate knowledge of its tertiary structure.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 026568118

Download citation: RISBibTeXText

PMID: 1820

DOI: 10.1098/rstb.1975.0072

Related references

Reversible inhibition in bimolecular rapid equilibrium random order enzyme systems. The effect of substrate-substrate and inhibitor-substrate interactions. Biochemical Journal 117(5): 997-1003, 1970

The interdependence of substrate and protein transformations in rhodanese catalysis. I. Enzyme interactions with substrate, product, and inhibitor anions. Journal of Biological Chemistry 248(21): 7376-7385, 1973

Enzyme-substrate binding interactions of NADPH-cytochrome P-450 oxidoreductase characterized with pH and alternate substrate/inhibitor studies. Biochemistry 32(43): 11539-11547, 1993

Separation methods applicable to the evaluation of enzyme-inhibitor and enzyme-substrate interactions. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 797(1-2): 175-190, 2003

Alliin Lyase from Garlic, Allium sativum: Investigations on Enzyme/Substrate, Enzyme/Inhibitor Interactions, and on a New Coenzyme. Planta Medica 55(5): 440-445, 1989

Homology modelling of human CYP2E1 based on the CYP2C5 crystal structure: Investigation of enzyme-substrate and enzyme-inhibitor interactions. Toxicology In Vitro 17(1): 93-105, 2003

The role of substrate and inhibitor carboxyl groups in enzyme substrate and enzyme inhibitor interaction of hyaluronidases. Biochemistry 38(6 PT 2): (1974), 1973

Enzyme-substrate (inhibitor) interactions as viewed from x-ray diffraction studies. Tanpakushitsu Kakusan Koso. Protein Nucleic Acid Enzyme 27(6): 855-869, 1982

A Discussion on the Physics and Chemistry of Biological Recognition || Enzyme Substrate and Inhibitor Interactions. Philosophical Transactions of the Royal Society of London Series B Biological Sciences 272(915): 87-97, 1975

Conformational aspects of inhibitor design: enzyme-substrate interactions in the transition state. Bioorganic and Medicinal Chemistry 7(5): 647-652, 1999

Role of the carboxyl groups in the substrate and in the inhibitors in the enzyme-substrate and enzyme-inhibitor interaction of hyaluronidases. Biokhimiia 38(6): 1237-1242, 1973

The role of carboxyl groups of the substrate and inhibitors in enzyme substrate and enzyme inhibitor interaction of hyaluronidases. Biokhimiya 38(6): 1237-1242, 1973

Secondary enzyme-substrate interactions: kinetic evidence for ionic interactions between substrate side chains and the pepsin active site. Biochemistry 27(13): 4827-4834, 1988

Gas-phase models of enzyme-substrate interactions The effects of hydrogen-bonding interactions on substrate ionization potentials. Abstracts of Papers American Chemical Society 222(1-2): COMP115, 2001

Conformational aspects of interactions of beta trypsin with substrates and pancreatic trypsin inhibitor i. conformational properties of residues in enzyme active center and structure of nonbonded enzyme substrate complex. Molekulyarnaya Biologiya (Moscow) 20(1): 102-119, 1986