Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites.

António J M Ribeiro,Gemma L Holliday,Jonathan D Tyzack,Nicholas Furnham,Katherine Ferris,Janet M Thornton

doi:10.1093/nar/gkx1012

Abstract

M-CSA (Mechanism and Catalytic Site Atlas) is a database of enzyme active sites and reaction mechanisms that can be accessed at www.ebi.ac.uk/thornton-srv/m-csa. Our objectives with M-CSA are to provide an open data resource for the community to browse known enzyme reaction mechanisms and catalytic sites, and to use the dataset to understand enzyme function and evolution. M-CSA results from the merging of two existing databases, MACiE (Mechanism, Annotation and Classification in Enzymes), a database of enzyme mechanisms, and CSA (Catalytic Site Atlas), a database of catalytic sites of enzymes. We are releasing M-CSA as a new website and underlying database architecture. At the moment, M-CSA contains 961 entries, 423 of these with detailed mechanism information, and 538 with information on the catalytic site residues only. In total, these cover 81% (195/241) of third level EC numbers with a PDB structure, and 30% (840/2793) of fourth level EC numbers with a PDB structure, out of 6028 in total. By searching for close homologues, we are able to extend M-CSA coverage of PDB and UniProtKB to 51 993 structures and to over five million sequences, respectively, of which about 40% and 30% have a conserved active site.

Highlights

Enzymes are the macromolecules that catalyze the chemical reactions of life
47.2% (262 310) of the 555 426 reviewed Swiss-Prot entries and 13.5% (12 050 143) of the complete UniProtKB dataset are annotated as enzymes, the latter figure primarily reflecting incomplete knowledge and annotation
We provide annotation for the associated protein sequences and structures, and when appropriate, we link to the databases mentioned above

Summary

Introduction

Enzymes are the macromolecules that catalyze the chemical reactions of life. The study of enzymes draws from the fields of biochemistry, genomics, protein structure, organic chemistry, computational chemistry, thermodynamics, and metabolomics, amongst others. These datasets have been helpful to explore overall themes related to enzyme mechanisms such as the evolution of new chemical function and the roles of specific catalytic residues, cofactors, and metal ions in the chemistry of life [28,29,30].

Results

Conclusion