Structure of enzyme domain involved in synthesis of natural products
Janet Smith group (University of Michigan) and collaborators
Janet Smith's group from the University of Michigan used
the beamline automounter to screen ~48 crystals in ~4 hrs to solve the
structure of the ECH2 domain of CurF from Lyngbya majuscula. CurF
ECH2 is a decarboxylase involved in the introduction of a
cyclopropyl ring in the biosynthesis of the natural product curacin A, which
is a potent cytotoxic agent. The structure was solved with a 3-wavelength
MAD data set using selenomethionine-labeled protein on beamline 23ID-B. The
structure demonstrated that CurF ECH2 has a crotonase fold, and
substrate modeling into the active site facilitated testing of active site
residues. This new structure has provided insights into β-branching in
polyketide synthesis as described in a manuscript submitted for publication.
Figure: View of CurF ECH2 monomer
demonstrating crotonase superfamily fold and active site chamber highlighted
with red asterisk.
Geders, TW, Gu, L, Mowers, JC, Liu, H, Gerwick, WH, Hakansson, K, Sherman,
DH, Smith, JL. "Crystal Structure of the ECH2 Catalytic Domain of
CurF from Lyngbya majuscula: Insights into a Decarboxylase Involved in
Polyketide Chain β-Branching", J. Biol. Chem. 282 (49), 35954-35963
(2007). DOI: 10.1074/jbc.M703921200.