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Figure 8.
Figure 8. Scheme of hE1b-Catalyzed Reactions Emphasizing
the Role of Tyr113-a as the Central Regulatory Conformational
Switch
(A) Prior to substrate binding, the side chain of
Tyr113-a, the switch turn (indicated by Q112|Y113|R114), and the
adjacent LBD binding region are in the S conformation.
(B)
Substrate binding displaces the Tyr113-a side chain and forces
it into the P conformation, where it establishes a hydrogen bond
to the terminal phosphate group in the ThDP cofactor and
additional interactions with the sulfur in the thiazolium ring
(dashed lines). Simultaneously, the switch turn is remodeled,
whereupon the adjacent LBD binding region adopts a
higher-affinity state for LBD.
(C and D) After, or
concomitant with, (C) decarboxylation, LBD binds to hE1b,
followed by (D) the transfer of an acyl moiety, derived from the
degradation of valine, leucine, or isoleucine to lipoic acid
(LA).
TZ, thiazolium ring; AP, aminopyrimidine ring; B,
general base.
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