Reaction Attributes

Reaction attributes can be described as basic processes involved in the reaction, or an overall effect which occurs during the course of the reaction. The following are allowable reaction attributes in MACiE:

• Bond Cleavage
• Bond Formation
• Bond Order Change
• Bond Polarisation
• Charge Delocalisation
• Cofactor Regenerated
• Cofactor Used
• Coordination to a metal species
• Cyclisation - The formation of a ring compound from a chain by the formation of a new bond.
• Deamination - Ammonia is one of the products of the reaction. It may be produced either through elimination, or some other mechanism.
• Decarboxylation - A reaction in which carbon dioxide is eliminated from one of the reacting species.
• Decoordination from a metal species
• Decyclisation - The formation of a chain compound from a ring by the cleavage of an existing bond.
• Dehydration - A reaction in which water is one of the products of the reaction.
• Dephosphorylation - A reaction during which a phosphate moiety is a product of the reaction. This can be anything from a monophosphate to a triphosphate.
• Electron Relay
• Enzyme-Substrate Bond Cleavage
• Enzyme-Substrate Bond Formation
• Hydride Relay
• Hydrogen Relay
• Hydrolysis - A reaction in which water is involved in the rupture of one or more bonds in the reactant.
• Enzyme is Not Regenerated
• Inferred Step - A reaction step that is not explicitly stated in the literature, but which can be inferred from the literature.
• Intermediate Collapse
• Intermediate Formation
• Intermediate Terminated
• Product Formed
• Proton Relay
• Reaction occurs Outside the Enzyme
• Returning the Enzyme to its Ground State
• Schiff Base formation - The mechanism of forming Schiff bases is also known as a Schiff condensation. This is a multi-step reaction and as such we only term the final step the actual formation, e.g.
  

  

• Substrate Used

Bond Formation and Bond Cleavage

Both these reaction attributes require the user to specify the identity of the bonds involved. Due to the lack of atom-atom mapping in MACiE, especially in ISIS/Base, it is enough to simply state the type of bond, i.e. a C-H bond is formed, two O-H bonds are cleaved, a C-S bond is formed and an S-H bond cleaved, etc. It should be noted that only the first and last of the bond changes involved in a proton relay are included in bonds formed, cleaved or bond order changes.

Bond Order Change

Bond order change has special semantics. Whilst bond formed and cleaved is a simple list of the bond type identities, bond order changed lists the bond's type in the substrate and its order followed by the bond's type in the product and its new order. E.g. substrate-C-O, 1, product-C=O, 2, which translates to a C single bond O in the substrate is changing to a C double bond O in the product. If there are multiple bond order changes, unlike group transfers (listed from, from, to, to), bond order changes are: from, to, from, to. E.g. substrate-C-O, 1, productC=O, 2, substrate2-C=C, 2, product2-C-C, 1

Bond Polarisation

Bond polarisation is defined as the formation of charge over a bond, as opposed to specific atoms. They are rare in MACiE and only assigned when it is explicit in the literature reference. However, there are some cases in which the bond is clearly polarised, and in these cases, bond polarisation has been used and the user is required to define which bond is polarised.

Charge Delocalisation

Charge delocalisation has a limited use. Unfortunately it is not possible to draw the delocalisation of charge in ISIS and so, wherever possible, charge is drawn on specific atoms. Thus it is preferable for the bond order changes to be annotated explicitly. However, this is not always feasible or preferable and when this is the case, the user is expected to define which atoms are involved in a simple list.

Cofactor Used and Regenerated

These reaction attributes are analogous to substrate used and product generated, but they are specifically for reactions in which cofactors are used. Cofactor used is stated in the first step in which a cofactor (as stated in the overall reaction) is used, cofactor regenerated is stated in the step in which the cofactor is returned to its starting state.

Coordination To and Decoordination From a Metal Species

Coordination and decoordination refer in MACiE only to the formation (or destruction) of a metal-ligand coordinate bond. Coordination is when the ligand first binds to the metal, decoordination is when the ligand to metal `bond' is cleaved.

Enzyme-Substrate Bonds

This reaction attribute is included to explicitly state that in any given step a covalent bond is being formed or cleaved between the enzyme and the substrate. Whilst the bond formed (or cleaved) attribute will contain the enzyme-substrate bond, due to the lack of mapping it is not possible to automatically define which bond that is, hence, the use of a separate reaction attribute. No further information is given as to the identity (or type) of the enzyme-substrate bond.

Enzyme-substrate bond formation and cleavage refers to any case in which a bond is formed, or cleaved, to a species which is part of the enzyme. Thus, if a small molecules is eliminated from from an enzyme-substrate complex it is called an ESCleavage.

Electron, Hydride, Hydrogen and Proton Relay

These attributes are used when an electron, proton, hydride or hydrogen relay occurs in the enzyme, either through an amino acid residue, or a free chemical species present in the active site, such as water. Although they are specified under the function of an amino acids involved, it is necessary to specify them as reaction attributes as there are some instances when the relay is not through an amino acid residue. When this is the case there is no other way to define them as the bond changes involved are not counted.

Intermediate Collapse, Formation and Termination

An intermediate is defined as a chemical species with a lifetime appreciably longer than a molecular vibration that is formed from the reactants and reacts further to give the products of a chemical reaction, or another intermediate.

A reaction in which an intermediate collapses is given the reaction attribute of intermediate collapse. This occurs when a single intermediate species collapses into two other intermediate species. Intermediate collapse requires further input. The user is required to identify the intermediate collapsed in both the above cases. There is no differentiation between the two cases of intermediate collapse.

A reaction in which an intermediate is formed is given the reaction attribute of intermediate formation. The user is then required to identify the intermediate formed.

The collapse of an intermediate species into a product of the overall reaction is an intermediate termination, and requires no further input.

Product Formed and Substrate Used

This is only present when a substrate or product stated in the overall reaction reacts or is formed in a step.

Returning the Enzyme to its Ground State

The return attribute is only used when the enzyme's native state is regenerated. Often, the final step of an enzyme mechanism, as presented in the literature, ends with the enzyme in a non-native state, in these cases inferred return steps should be added, and annotated as returns in the comment field in the reaction stage. Sometimes it is not possible to infer a return step, in which case the attribute not returned is assigned to the final stage of the reaction. In cases where there is no change to the amino acid residues involved, there should be no information on the return entered into the annotation.

Return is defined as: the enzyme is returned to its ground state and/or is ready to undergo another round of catalysis

Reaction Occurs Outside the Enzyme

The reaction attribute outside deals with reactions that are necessary to complete the overall reaction as described by the EC, but do not occur within the enzyme. Reactions which have this attribute should never have any other annotation.