Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis

Han, Lu; Singh, Shanteri; Thorson, Jon S.; Phillips, George N.

doi:10.1063/1.4941368

Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis

Journal Article · Thu Feb 18 00:00:00 EST 2016 · Structural Dynamics

DOI:https://doi.org/10.1063/1.4941368· OSTI ID:1419071

Han, Lu ^[1]; Singh, Shanteri ^[2]; Thorson, Jon S. ^[2]; Phillips, George N. ^[1]

Rice Univ., Houston, TX (United States)
Univ. of Kentucky, Lexington, KY (United States). Center for Pharmaceutical Research and Innovation

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.

View Accepted Manuscript (DOE)

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1419071

Journal Information:: Structural Dynamics, Journal Name: Structural Dynamics Journal Issue: 1 Vol. 3; ISSN SDTYAE; ISSN 2329-7778

Publisher:: American Crystallographic Association/AIPCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Loop dynamics of thymidine diphosphate-rhamnose 3'-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis

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