Table 3.

Residues in correctly predicted 3 top-ranked clusters

Structure	Function	Cluster
1ahc A	(RNA) glycosidase	$\underset{¯}{\text{R}},\underset{¯}{\ddot{\text{E}}},\ddot{\mathsf{\text{E}}},\underset{¯}{\mathsf{\text{Q}}}$
1bbs A	proteinase	$\underset{¯}{\ddot{\text{D}}},\underset{¯}{\ddot{\text{D}}}$
1bya A	O-glycosidase	$\underset{¯}{\ddot{\text{E}}},\underset{¯}{\mathsf{\text{R}}},\underset{¯}{\ddot{\mathsf{\text{E}}}},\mathsf{\text{P}}$
1cge A	metalloproteinase	$\underset{¯}{\ddot{\text{E}}}$
1djb A	hydrolase (β-lactamase)	$\underset{¯}{\text{K}},\underset{¯}{\text{E}}$
1hsi A	protease (HIV-2 retropepsin)	$\underset{¯}{\mathsf{\text{I}}}\left(\mathsf{\text{flaps}}\right)$
1hxf H	(serine) protease	$\underset{¯}{\ddot{\text{D}}}$
1ifb A	fatty acid binding	$\ddot{\text{R}},\text{E}$
1ime A	(inositol) phosphatase	$\underset{¯}{\ddot{\text{D}}},\underset{¯}{\ddot{\text{D}}},\underset{¯}{\ddot{\text{D}}}$
1krn A	hydrolase (fibrinolysin)	$\ddot{\text{K}}$
1l3f E	proteolysin	$\underset{¯}{\text{E}}$
1nna A	O-glycosidase	$\underset{¯}{\ddot{\text{K}}},\underset{¯}{\ddot{\text{E}}},\underset{¯}{\text{R}},\underset{¯}{\ddot{\text{E}}},\underset{¯}{\text{Q}}$
1npc A	(metallo)protease	$\underset{¯}{\text{E}},\underset{¯}{\mathsf{\text{E}}}$
1pdy A	enolase	$\underset{¯}{\text{K}},\underset{¯}{\mathsf{\text{R}}},\underset{¯}{\mathsf{\text{Q}}}$
1psn A	(acid) proteinase	$\underset{¯}{\ddot{\text{D}}},\underset{¯}{\ddot{\text{D}}}$
1pts A	azobenzoic acid binding	$\underset{¯}{\mathsf{\text{D}}}$
1qif A	(acetylcholin)esterase	$\underset{¯}{\ddot{\mathsf{\text{E}}}}$
1stn A	(phosphodi)esterase	$\underset{¯}{\text{R}},\underset{¯}{\ddot{\text{D}}}$
1ypi A	(triosephosphate) isomerase	$\underset{¯}{\text{K}},\underset{¯}{\mathsf{\text{E}}}$
2cba A	lyase (anhydrase)	$\underset{¯}{\ddot{\mathsf{\text{E}}}},\underset{¯}{\ddot{\text{E}}}$
2ctb A	hydrolase (carboxypeptidase)	$\underset{¯}{\text{E}}$
2fbp B	(fructose bis)phosphatase	$\underset{¯}{\text{K}},\underset{¯}{\ddot{\text{E}}},\underset{¯}{\text{D}},\underset{¯}{\ddot{\text{D}}},\underset{¯}{\ddot{\text{E}}}$
2sil A	hydrolase (neuraminidase)	$\ddot{\mathsf{\text{E}}},\text{Q},\text{Q},\underset{¯}{\ddot{\text{R}}},\underset{¯}{\ddot{\text{R}}}$
3app A	(acid) proteinase	$\underset{¯}{\ddot{\text{D}}}$
3p2p A	(carboxyl)esterase	$\mathsf{\text{R}},\underset{¯}{\text{D}}$
3ptn A	hydrolase (tripsin)	$\underset{¯}{\text{D}}$
3tms A	(methyl)transferase	$\underset{¯}{\ddot{\text{E}}},\underset{¯}{\text{N}},\underset{¯}{\mathsf{\text{Q}}}$
5dfr A	(folic acid) reductase	$\underset{¯}{\text{D}}$
8adh A	dehydrogenase	$\underset{¯}{\text{E}},\underset{¯}{\ddot{\text{D}}}$
8rat A	hydrolase (ribonuclease)	$\underset{¯}{\ddot{\text{K}}},\text{Q}$

Residues are sorted in rows according to decreasing unexpectedness. Residues of the highest evolutionary conservation scores according to the ConSurf-DB [66] are underlined; residues indicated as functional by Thematics [25] have overbars; bold residues are annotated as catalytic in the Catalytic Sites Atlas (CSA) [58]. (Two chains of non-enzymatic functions are unannotated in the CSA.)