Catalytic Mechanism in
Artificial Metalloenzyme: QM/MM
Study of Phenylacetylene Polymerization by Rhodium Complex Encapsulated
in <i>apo</i>-Ferritin
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Abstract
Artificial metalloenzyme, composed of metal complex(es)
and a host
protein, is a promising way to mimic enzyme catalytic functions or
develop novel enzyme-like catalysis. However, it is highly challenging
to unveil the active site and exact reaction mechanism inside artificial
metalloenzyme, which is the bottleneck in its rational design. We
present a QM/MM study of the complicated reaction mechanism for the
recently developed artificial metalloenzyme system, <b>(Rh(nbd)·</b><i><b>apo</b></i><b>-Fr</b>) (nbd = norbornadiene),
which is composed of a rhodium complex [Rh(nbd)Cl]<sub>2</sub> and
the recombinant horse L-chain <i>apo</i>-Ferritin. We found
that binding sites suggested by the X-ray crystal structure, i.e.,
sites A, B, and C, are only precursors/intermediates, not true active
sites for polymerization of phenylacetylene (PA). A new hydrophobic
site, which we name D, is suggested to be the most plausible active
site for polymerization. Active site D is generated after coordination
of first monomer PA by extrusion of the Rh<sup>I</sup>(PA) complex
to a hydrophobic pocket near site B. Polymerization occurs in site
D via a Rh<sup>I</sup>-insertion mechanism. A specific “hydrophobic
region” composed by the hydrophobic active site D, the nonpolar
4-fold channel, and other hydrophobic residues nearby is found to
facilitate accumulation, coordination, and insertion of PA for polymerization.
Our results also demonstrate that the hydrophobic active site D can
retain the native regio- and stereoselectivity of the Rh-catalyzed
polymerization of PA without protein. This study highlights the importance
of theoretical study in mechanistic elucidation and rational design
of artificial metalloenzymes, indicating that even with X-ray crystal
structures at hand we may still be far from fully understanding the
active site and catalytic mechanism of artificial metalloenzymes