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. Author manuscript; available in PMC: 2017 Aug 1.
Published in final edited form as: Ann N Y Acad Sci. 2016 Jul 2;1378(1):41–49. doi: 10.1111/nyas.13128

Table 1.

Comparison of ligand-associated spectral shifts of acrylodan attached at one of five positions in mAChE with ligand-associated variability of distances between backbone Cα atoms at each position and the Cα of the active serine observed from X-ray structures.

Ligand Leu 76 (Gln 74)
Ω Loop gorge rim		 Glu 81 (Ser 79)
Ω Loop top outside		 Glu 84 (Glu 82)
Ω Loop top outside		 Tyr 124 (Tyr 121)
Gorge “choke point”		 His 287 (Asn 280)
Acyl pocket loop, PAS
Spectral
shift
(nm)		 Δ Distance
(complex-apo)
(Å)		 Spectral
shift
(nm)		 Δ Distance
(complex-apo)
(Å)		 Spectral
shift
(nm)		 Δ Distance
(complex-apo)
(Å)		 Spectral
shift
(nm)		 Δ Distance
(complex-apo)
(Å)		 Spectral
shift
(nm)		 Δ Distance
(complex-apo)
(Å)
mAChE m,hAChE TcAChE mAChE m,hAChE TcAChE mAChE m,hAChE TcAChE mAChE m,hAChE TcAChE mAChE m,hAChE TcAChE
Tacrine 4 — −0.2 21 — −0.2 33 — −0.1 −3 — 0.0 0 — −0.3
Edrophonium 4 — 0.1 21 — 0.0 33 — 0.1 0 — 0.1 0 — 0.0
Huperzine A 6 −0.6 −0.1 21 −0.2 0.0 33 −0.1 0.1 0 −0.2 0.0 0 −0.1 −0.1
BW284c51 3 — 0.0 21 — −0.1 35 — −0.2 −13 — 0.2 −14 — 0.2
Decamethonium 3 −0.7 0.0 21 −0.5 −0.4 28 −0.5 −0.2 −35 −0.3 0.2 −7 −0.1 0.2
Gallamine −4 −0.6 14 −0.1 9 −0.1 −25 −0.1 −14 −0.1
Fas2 0 −0.6 −0.6 21 −0.4 −0.6 35 −0.3 −0.2 −23 −0.1 0.1 −17 −0.1 −0.1
TFK+ 6 −0.3 0.3 21 0.0 −0.4 35 0.0 −0.3 3 0.0 0.1 0 0.1 0.3
Rivastigmine 0 — 0.0 −30 — −0.5 20 — −0.3 −4 — 0.0 0 — 0.2
Sarin 3 −0.4 — 11 −0.1 — 23 −0.2 — 0 0.0 — 0 0.0 —
VX −5 −0.4 — 4 0.1 — 19 0.0 — −11 0.0 — 0 0.0 —
DFP −5 −0.4 — −14 0.0 — 18 0.0 — −10 0.0 — −3 0.2 —

Note: Comparison of ligand-associated spectral shifts of acrylodan12,13 covalently attached at one of five positions in mAChE (76,81,84,124, and 287; TcAChE numbering is shown in parentheses) with ligand-associated variability of distances between backbone Cα atoms at each position and the Cα of the active serine (Δdistance = (distance between Cαposition and CαSer203)complex − (distance between Cαposition and CαSer203)apo) observed from X-ray structures. Distance differences for mouse AChE (mAChE) and human AChE (hAChE) X-ray structures were similar and were averaged (for complexes with same ligand) and are shown in the same column (as m,hAChE). Data for Torpedo californica AChE (TcAChE) structures are shown in a separate column consistent with higher similarity in the Cα backbone between mammalian AChEs (Cα RMSD ~ 0.6) compared to TcAChE and mAChE (Cα RMSD ~ 0.8).6 A list of the structures used in analysis is given in Table S1.