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Choosing a New MACiE Entry

Entering a new reaction into MACiE is a relatively complex process, first the mechanism should be checked to see if it is currently present in the database, and then the new entry can be put into the development version of MACiE, which is currently held in ISIS/Base. The development version of MACiE is ported across when the new mechanisms have been validated.

All entries in MACiE are chosen such that:

  1. There is a 3-dimensional crystal structure of the enzyme deposited in the Protein Databank (wwPDB). The crystal structure should:
    1. be the wild type, however, this is not always possible
    2. include any catalytic metal ions and any relevant cofactors
    3. the highest resolution structure available, where there is more than one crystal structure that fulfils the first two selection criteria.
    4. Finally, crystal structures that include either substrates, products, analogues of either the reactant, substrate or transition state are considered to be advantageous
  2. There is a relatively well understood mechanism available, or at least a chemically meaningful suggestion of a mechanism, which are taken from a variety of sources, including chemical studies, quantum mechanical calculations and structure studies. The mechanism included should always be supported by experimental evidence. It is ideal when there are both computational studies and experimental studies.
  3. The enzyme is non-homologous to anything currently in MACiE. This can initially be determined as being unique at the H level of the CATH code - a hierarchical classification system of protein domain structures (for more information on the CATH code, see the CATH website). However, if there is a homologue with a significantly different chemical mechanism, this new mechanism should be included in MACiE.
  4. The mechanism has not been seen previously in MACiE

Up to version 2 of MACiE, a further selection criteria was applied such that the EC sub-subclass (the third level of the EC number) of the enzyme should not have been previously included in the dataset (for a list of the EC sub-subclasses currently defined and their coverage see here. Further expansion will depend upon the various projects taking place with the database. However, we would ideally wish to populate MACiE such that we cover all the available CATH domains.

To further extend MACiE after version 2.0, we have not followed specific selection criteria, with new entries mostly being governed by interest within our own research groups as well as external user requests. For example, we have included members of specific families of enzymes of interest (e.g. the terpenoid synthases superfamily) and multiple representatives for cases where there are known multiple mechanisms associated with specific EC numbers (e.g. the haloperoxidases, EC If you would like to request an enzyme be added, please email a member of the team with as much detail as possible.

We have also now set up a GoogleDocs document called Possible New Entries, which lists available information on entries that have been requested, or identified as possible new entries for MACiE. This document should be kept up-to-date and used as the first port of call for identifying new entries.

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