title: Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis.
abstract: Structure analysis and ensemble refinement of the apo-structure of thymidine diphosphate (TDP)-rhamnose 3'-O-methyltransferase reveal a gate for substrate entry and product release. TDP-rhamnose 3'-O-methyltransferase (CalS11) catalyses a 3'-O-methylation of TDP-rhamnose, an intermediate in the biosynthesis of enediyne antitumor antibiotic calicheamicin. CalS11 operates at the sugar nucleotide stage prior to glycosylation step. Here, we present the crystal structure of the apo form of CalS11 at 1.89 Å resolution. We propose that the L2 loop functions as a gate facilitating and/or providing specificity for substrate entry or promoting product release. Ensemble refinement analysis slightly improves the crystallographic refinement statistics and furthermore provides a compelling way to visualize the dynamic model of loop L2, supporting the understanding of its proposed role in catalysis.
authors.affiliation: Biosciences at Rice, Rice University , Houston, Texas 77005, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences, University of Kentucky College of Pharmacy , Lexington, Kentucky 40536-0596, USA.
authors.forename: Shanteri
authors.initials: S
authors.lastname: Singh
authors.affiliation: Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences, University of Kentucky College of Pharmacy , Lexington, Kentucky 40536-0596, USA.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Thorson
authors.forename: George N
authors.initials: GN
authors.lastname: Phillips