title: Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate.
abstract: 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.
authors.affiliation: Biosciences at Rice, Rice University , 6100 Main St., Houston, Texas 77005, USA.
authors.forename: Hongnan
authors.initials: H
authors.lastname: Cao
authors.affiliation: Biosciences Division, Midwest Center for Structural Genomics, Argonne National Laboratory , Bldg. 446/Rm. A104, 970 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Kemin
authors.initials: K
authors.lastname: Tan
authors.affiliation: Biosciences at Rice, Rice University , 6100 Main St., Houston, Texas 77005, USA.
authors.forename: Fengbin
authors.initials: F
authors.lastname: Wang
authors.affiliation: Biosciences Division, Midwest Center for Structural Genomics, Argonne National Laboratory , Bldg. 446/Rm. A104, 970 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Lance
authors.initials: L
authors.lastname: Bigelow
authors.affiliation: Biosciences at Rice, Rice University , 6100 Main St., Houston, Texas 77005, USA.
authors.forename: Ragothaman M
authors.initials: RM
authors.lastname: Yennamalli
authors.affiliation: Biosciences Division, Midwest Center for Structural Genomics, Argonne National Laboratory , Bldg. 446/Rm. A104, 970 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Jedrzejczak
authors.affiliation: Biosciences Division, Midwest Center for Structural Genomics, Argonne National Laboratory , Bldg. 446/Rm. A104, 970 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Babnigg
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bingman
authors.affiliation: Biosciences Division, Midwest Center for Structural Genomics, Argonne National Laboratory , Bldg. 446/Rm. A104, 970 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, USA.
authors.forename: Madan K
authors.initials: MK
authors.lastname: Kharel
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, USA.
authors.forename: Shanteri
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, USA.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.affiliation: Biosciences at Rice, Rice University , 6100 Main St., Houston, Texas 77005, USA.
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips