CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.
|State||Published - May 1 2016|
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health Grant Nos. CA84374 (J.S.T.), U01GM098248 (G.N.P.), and GM094585 (A.J.) and the National Center for Advancing Translational Sciences (UL1TR000117). Results shown in this report are derived from work performed at 19-ID beamline of Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under Contract No. DEAC02-06CH11357.
© 2016 Author(s).
ASJC Scopus subject areas
- Condensed Matter Physics