Skip to content

M-CSA (Mechanism and Catalytic Site Atlas)

Summary

M-CSA is a hand-curated database of enzyme active sites and stepwise catalytic mechanisms, formed by merging two predecessor resources: MACiE (Mechanism, Annotation and Classification in Enzymes) and CSA (Catalytic Site Atlas). It fills a gap that sequence databases (UniProt), structure databases (PDB), and reaction databases (Rhea, KEGG) each leave open. None of these directly record how an enzyme's active site executes its chemistry, step by step.[1]

Scope and Coverage

At the time of its 2018 description, M-CSA contained 961 entries: 423 with full stepwise mechanism annotation and 538 with catalytic-site residue information only. Homology-based extension (searching for close structural/sequence homologues of curated entries) expands its effective coverage to 51,993 PDB structures and over five million UniProtKB sequences, of which roughly 40% and 30% respectively are estimated to have a conserved active site. Curated entries cover 81% of third-level EC numbers with a PDB structure, but only 30% of fourth-level (full, specific) EC numbers with a PDB structure — reflecting that M-CSA's curation effort, while extensive, is necessarily finite relative to the full breadth of enzyme chemistry.[1]

Why This Matters for Catalysis Prediction

M-CSA's curated mechanisms are the closest thing available to ground truth for "this residue does this chemical step" — as distinct from a docking score, a co-folded pose, or a kinetic parameter, none of which directly assert that a specific residue performs a specific catalytic act. Homology-based transfer of an M-CSA mechanism to an uncurated homologue is a standard practical shortcut, but it can fail for divergent chemistries where local active-site geometry, not overall fold conservation, controls the reaction.

See Also

Citations

[1] Ribeiro, A.J.M., Holliday, G.L., Furnham, N., Tyzack, J.D., Ferris, K., Thornton, J.M. (2018). Mechanism and Catalytic Site Atlas (M-CSA): a database of enzyme reaction mechanisms and active sites. Nucleic Acids Research, 46(D1), D618–D623. Supports: all coverage and scope figures above. Location: Abstract; Introduction.