Article | REF: PHA1502 V1

Structural Enzymology

Authors: Serge KIRKIACHARIAN, Julien DUMOND

Publication date: July 10, 2024

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ABSTRACT

Understanding how enzymes work requires the knowledge of the stereoelectronic structure of these macromolecules formed from the assembly of amino acids espacially through the evolution of weak bonds. Various biochemical and physicochemical techniques used to determine their different levels of structure from primary to quaternary are discussed. Finally, the article includes the study of three enzymes with different structural characteristics: carbonic anhydrase, glycogen phosphorylase and human immunodeficiency virus (HIV) protease.

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AUTHORS

  • Serge KIRKIACHARIAN: Doctor of Physical Sciences – Pharmacist - Professor Emeritus of Therapeutic Chemistry, - Faculty of Pharmaceutical and Biological Sciences, Université Paris-Sud - Honorary Head of Department, Paris Hospitals, France

  • Julien DUMOND: Doctor in Virology and Enzymology - Consultant to pharmaceutical companies, Metz, France

 INTRODUCTION

Enzymes are proteins. The term protein comes from the prefix “proto-”, meaning first, in relation to the importance of these biological macromolecules in every living matter, and second the fact that before 1950 most scientists gave more credence to the paradigm of proteins at the origin of life than to that of nucleic acids at the basis of living organisms.

Like all proteins, an enzyme is encoded by at least one gene. Its structure is made up of a chain of amino acids that take on a precise spatial conformatio, in order to allow the realization of a specific chemical reaction. The enzyme is therefore a functional polymer of at least 50 amino acids, depending on the definition given to a protein. Thanks to ribosomes, it is synthesized during a translation process initiated in the cytoplasm of a cell or in the mitochondrial matrix from mRNA (messenger ribonucleic acid) containing the genetic information.

Fundamental and applied researches dedicated to enzymes are very extensive in a variety of fields. Numerous companies and laboratories are investing considerable human and financial resources in characterizing these catalysts and exploiting them to make the best use of them for the human beings. Before using or targeting an enzyme, purification protocols must be clearly established, and knowledge of its structure and physicochemical properties fully controlled.

Enzymes were first studied for their involvement in the metabolism of living organisms. Initially, these molecules easily accessible from liquids or simple organisms were scrutinized. When purification processes were improved, many enzymes were isolated and characterized. Their possible applications by and for human beings could then be performed. At present, there are three major areas of industrial applications or targeting of enzymes, which require mastery of many related fields:

  • pharmaceutical and cosmetics companies to whom the design of drugs and wellness products require the knowledge of organic chemistry, molecular modeling, pharmacology, ADMEtox (administration, distribution, metabolism, excretion and toxicology), and galenics… It could be emphasized that pharmaceutical companies have developed over the last years the most complete panel possible of enzyme tests (kinetics) or receptor tests (affinity and functional tests;

  • agri-food companies where the manufacture of products intended for consumption involves mastery of microbiology, plant biology, metabolism and the knowledge of bioreactors…;

  • environment-related companies with a view to generating environmentally-friendly products...

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KEYWORDS

structures   |   enzymes   |   bonds   |   biochemical and physicochemical techniques


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Structural enzymology