Table 1.

Listing and residue number correlation of amino acids with primary catalytic roles as inferred from model HADs L-Dex YL (PDB ID 1JUD), DhlB (1QQ5) and DehIVa (2NO5).

Enzyme	L-Dex YL	DhlB	DehIVa	RSc1362	PA0810	Rha0230	Bpro0530	ST2570
SwissProt ID	Q53464	Q60099	Q51645	Q8XZN3	Q9I5C9	Q0SK70	Q12G50	Q96XE7
Nucleophile	D10	D8	D11	D10	D7	D21	D10	D7
Halide-binding	R41a	R39	R42	R41	R44	R58	R41	R23
	q44 b	q42	q45	q44	Y47	Y61	q44	q26
	N119	N115	q45	N123	N122	N139	N119	N96
	W179 c	F175	W180	W183	Y180	G197d	W179	F154
Carboxylate binding	S118	S114	S119	S122	S121	S138	S118	S95
Hydrolysis of covalent ester intermediate	T14e	T12	T15	T14	T11	T25	T14	T11
	S175ef	S171	S176	S179	A176g	A193g	S175	S150
	N177ef	N173	N178	N181	H178	H195	N177	N152
	D180fgh	D176	D181	D184	D181	D198	D180	D155
Multifunction	K151i	K147	K152	K155	K152	K169	K151	K128
Stabilizes Asp180	Y157	Y153	Y158	Y161	Y158	Y175	Y157	Y134

^aThe conserved arginine is also proposed to recruit the substrate in a ‘lockdown’ mechanism based on its highly dynamic nature.

^bThe lower case letter q is meant to indicate the glutamine amino acid found in most HADs at this position. Its side chain invariably points away from the active site and is not expected to support catalysis. A grey background indicates residues that are unique to the new PA0810/Rha0230 subfamily; Y47 and Y61, respectively, are in positions to interact with the halide atom.

^cAlthough the chemical identity of the residues in this position changes their aromatic character is conserved with the exception of

^dRha0230, which lacks the conserved aromatic side chain that interacts with the halide.

^eForms the oxyanion hole.

^fBinds the catalytic water.

^gActivates the catalytic water.

^hLacks the hydroxyl group of the conserved serine, binding of catalytic water may be taken over by the histidine found two residues downstream.

ⁱOrients the aspartate nucleophile, binds substrate and stabilizes Asp180 (L-Dex YL). A green background indicates the three defluorinating enzymes.