|
Figure 1.
Figure 1. (a) The substrate molecules of mammalian Amacr. The
covalent structures of pristanoyl-CoA,
3,7,12-trihydroxycoprostanoyl-CoA and ibuprofenoyl-CoA are
shown. The methyl group attached to the chiral C^α atom is
referred to as the 2-methyl moiety. Amacr interconverts the
chirality of this C^α atom. (b) The covalent structures of the
substrate analogues acetyl-CoA and acetoacetyl-CoA. The
conformation of the acetoacetyl moiety shown at the left
concerns the conformation that allows for internal hydrogen
bonding. The rotamer at the right visualizes the observed mode
of binding in the structure of the acetoacetyl-CoA MCR complex.
(c) The reaction catalyzed by MCR. The catalytic interconversion
of the two enantiomers takes place in the enzyme active site by
a 1,1-proton transfer involving a catalytic acid/base-pair,
which in MCR is His126 (base B[1]) and Asp156 (base B[2]). In
the anionic intermediate, the C^α atom is planar and a negative
charge develops on the thioester oxygen atom.
|
