Loop dynamics of thymidine diphosphate-rhamnose 3′-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
AIP Publishing LLC and ACA
2016-01-01
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| Series: | Structural Dynamics |
| Online Access: | http://dx.doi.org/10.1063/1.4941368 |
| _version_ | 1828481402681688064 |
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| author | Lu Han Shanteri Singh Jon S. Thorson George N. Phillips Jr. |
| author_facet | Lu Han Shanteri Singh Jon S. Thorson George N. Phillips Jr. |
| author_sort | Lu Han |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T07:56:05Z |
| format | Article |
| id | doaj.art-e9b5a8dd56054a49b20528b9a14411f4 |
| institution | Directory Open Access Journal |
| issn | 2329-7778 |
| language | English |
| last_indexed | 2024-12-11T07:56:05Z |
| publishDate | 2016-01-01 |
| publisher | AIP Publishing LLC and ACA |
| record_format | Article |
| series | Structural Dynamics |
| spelling | doaj.art-e9b5a8dd56054a49b20528b9a14411f42022-12-22T01:15:13ZengAIP Publishing LLC and ACAStructural Dynamics2329-77782016-01-0131012004012004-810.1063/1.4941368004692SDYLoop dynamics of thymidine diphosphate-rhamnose 3′-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesisLu Han0Shanteri Singh1Jon S. Thorson2George N. Phillips Jr.3 Biosciences at Rice, Rice University, Houston, Texas 77005, USA Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0596, USA Center for Pharmaceutical Research and Innovation, Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0596, USA Biosciences at Rice, Rice University, Houston, Texas 77005, USAStructure 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.http://dx.doi.org/10.1063/1.4941368 |
| spellingShingle | Lu Han Shanteri Singh Jon S. Thorson George N. Phillips Jr. Loop dynamics of thymidine diphosphate-rhamnose 3′-O-methyltransferase (CalS11), an enzyme in calicheamicin biosynthesis Structural Dynamics |
| title | Loop dynamics of thymidine diphosphate-rhamnose
3′-O-methyltransferase (CalS11), an enzyme in
calicheamicin biosynthesis |
| title_full | Loop dynamics of thymidine diphosphate-rhamnose
3′-O-methyltransferase (CalS11), an enzyme in
calicheamicin biosynthesis |
| title_fullStr | Loop dynamics of thymidine diphosphate-rhamnose
3′-O-methyltransferase (CalS11), an enzyme in
calicheamicin biosynthesis |
| title_full_unstemmed | Loop dynamics of thymidine diphosphate-rhamnose
3′-O-methyltransferase (CalS11), an enzyme in
calicheamicin biosynthesis |
| title_short | Loop dynamics of thymidine diphosphate-rhamnose
3′-O-methyltransferase (CalS11), an enzyme in
calicheamicin biosynthesis |
| title_sort | loop dynamics of thymidine diphosphate rhamnose 3 o methyltransferase cals11 an enzyme in calicheamicin biosynthesis |
| url | http://dx.doi.org/10.1063/1.4941368 |
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