TCD Celebrates Landmark Anniversary as World Centre for Enzyme Classification

Posted on: 30 August 2007

Trinity College Dublin this year celebrates the 15th anniversary as the world centre for enzyme classification. The laboratory of Professor Keith Tipton at the School of Biochemistry and Immunology, TCD, was designated by the International Union of Biochemistry and Molecular Biology (IUBMB) as the world centre for the nomenclature and classification of enzymes in 1992.

“Enzyme classification is of fundamental importance to the scientific and medical communities. Through this unambiguous identification of enzymes many branches of translational research, including drug design and biotechnology, are facilitated,” according to Professor Tipton.

 Enzymes, which are the most studied of biological molecules, constitute nature’s toolkit for making and destroying the molecules required for the life, growth and death of all organisms. They can catalyse remarkably complex and specific chemical transformations under physiological conditions. Many commonly used drugs, including Asprin, antibiotics (such as penicillin and vancomycin), the cholesterol-lowering Statins, the ACE inhibitors, Viagra and many anticancer and anti-HIV drugs, are inhibitors of specific enzymes. Because the Enzyme Nomenclature system classifies enzymes in terms of the reactions that they catalyse (a functional classification), rather than their structures, it is becoming increasingly important in bioinformatics, functional genomics and systems biology.

Over 35 major databases worldwide use the enzyme data generated by TCD as a core part of their datasets. These include Chemical Abstracts (USA), Kyoto Encyclopedia of Genes and Genomes (KEGG; Japan), the BRENDA Comprehensive Enzyme Information System (Germany) and the MetaCyc Encyclopedia of Metabolic Pathways (USA). Individual scientists and students also use this enzyme data extensively.   

As the world centre for enzyme classification, Professor Tipton and his team at the TCD School of Biochemistry and Immunology, Drs Sinead Boyce and Andrew McDonald, provide a name for each enzyme as well as an EC number, a four-digit identifier to the enzyme which uniquely defines its function. They also provide important information about the enzymes such as their reactions catalysed, other names by which the enzyme has been known, a systematic name, comments, references and links to other relevant databases as well as a glossary which provides further definition of lesser-known biochemical terms.

All EC number assignments prepared at TCD, are circulated to members of the IUBMB Nomenclature committee and made available, through the worldwide web, to members of the scientific community for comment before finally being incorporated into the Official Enzyme list.

The world centre database at TCD currently holds approximately 4000 current enzyme entries, plus more than 1000 records for enzyme entries that have been modified as a result of new discoveries. All suggestions for new enzymes to be added and for modifications of existing entries, which arise from new research or analysis, are sent directly to  TCD where the detailed entries, as well as the assignments of the EC classification numbers, are prepared and put on its website for public review before they are made official.

Over the past 15 years, Professor Tipton’s laboratory has introduced significant changes in nomenclature of enzymes.  Until 1999, updates to the Enzyme List occurred only once a year and were published in the European Journal of Biochemistry.  His team introduced additional supplements which were published electronically in order to increase the efficiency of the evaluation process.  And now there is a continuous rolling process of adding and approving new enzymes.

An enhanced enzyme database, called ExplorEnz, was also developed in TCD and this now stores and disseminates the enzyme data to the IUBMB web site and the major databases. It also links each enzyme to the corresponding material in the major databases that provide additional information, such as gene annotation, enzyme-inhibitor interactions, and functional properties.

Professor Tipton and his team also developed and host a suite of web applications for automating the correct incorporation of new material of the ExplorEnz data.  As the first of its kind, it includes a method for automating the formatting of chemical names, a feature of the curatorial tools that greatly simplifies the data-entry process. ExplorEnz has also been supplemented by databases and applications for tracing metabolic processes, which should facilitate the selection of drug targets, and for identifying functions for newly discovered proteins that result from genetic studies. These further enhance the international standing of TCD as a centre for bioinformatics and Systems Biology.