Table 2.

Splitting events that separate ECs that use sites with different nuclearity (i.e. a different number of metal ions within the site). EC numbers associated to enzymes that use sites with different nuclearity e.g. in different organisms, were reported on the same line, with a list of all sites separated by “/”. See the caption to Table 1 for a further description of the contents in the various columns.

CATH code	Metal role conserved	Redox role	Ion(s)	EC diversity	EC(s)	Mechanism
3.40.630.10	Yes	No	Zn/Zn2	L2	3.5.1.18	Increases acidity and nucleophilicity of a water molecule and increases electrophilicity of substrate
			Zn2		3.4.11.10 3.4.11.4 3.5.1.14
			Zn		3.4.17.1
2.60.40.420	Yes	Yes	Cu	L2	1.7.2.1	Electron relay to substrate
			Cu2		1.10.3.2
3.20.20.150	Yes	No	Zn/Mn	L1	4.2.1.8 5.3.1.22	Increases the acidity of the substrate
			Divalent2		5.3.1.5 5.3.1.14
			Divalent3		3.1.21.2
3.20.20.60	Yes	No	Mg2	L1	2.7.1.40	Stabilizes charges and increases substrate acidity
			Mg		5.4.2.9 2.7.3.9 2.1.2.11 2.7.9.2 4.1.3.1
3.40.720.10	No	No	Mn2	L1	5.4.2.7	Increases nucleophilicity of a water molecule and electrophilicity of the phosphate moiety in the substrate
			Zn2		3.1.3.1
			Mn/Co Ca/Mg		5.4.2.1 3.1.6.1 3.1.6.8 3.1.6.12 3.1.6.2	Stabilizes charges and increases electrophilicity of substrate
3.20.20.140	No	No	Zn2 Zn2/Fe2 Ni2	L1	3.5.2.3 3.4.13.19 3.5.1.25 3.5.4.2 3.5.1.5	Increases electrophilicity of the substrate and nucleophilicity of a second substrate or functional group.
			Zn		5.3.1.12	Increases acidity of substrate