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Title: Structure of the Bacillus anthracis dTDP- L -rhamnose-biosynthetic enzyme glucose-1-phosphate thymidylyltransferase (RfbA)

Abstract

L-Rhamnose is a ubiquitous bacterial cell-wall component. The biosynthetic pathway for its precursor dTDP-L-rhamnose is not present in humans, which makes the enzymes of the pathway potential drug targets. In this study, the three-dimensional structure of the first protein of this pathway, glucose-1-phosphate thymidylyltransferase (RfbA), fromBacillus anthraciswas determined. In other organisms this enzyme is referred to as RmlA. RfbA was co-crystallized with the products of the enzymatic reaction, dTDP-α-D-glucose and pyrophosphate, and its structure was determined at 2.3 Å resolution. This is the first reported thymidylyltransferase structure from a Gram-positive bacterium. RfbA shares overall structural characteristics with known RmlA homologs. However, RfbA exhibits a shorter sequence at its C-terminus, which results in the absence of three α-helices involved in allosteric site formation. Consequently, RfbA was observed to exhibit a quaternary structure that is unique among currently reported glucose-1-phosphate thymidylyltransferase bacterial homologs. These structural analyses suggest that RfbA may not be allosterically regulated in some organisms and is structurally distinct from other RmlA homologs.

Authors:
; ; ; ORCiD logo; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIAID
OSTI Identifier:
1408122
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section F, Structural Biology Communications; Journal Volume: 73; Journal Issue: 11
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Baumgartner, Jackson, Lee, Jesi, Halavaty, Andrei S., Minasov, George, Anderson, Wayne F., and Kuhn, Misty L. Structure of the Bacillus anthracis dTDP- L -rhamnose-biosynthetic enzyme glucose-1-phosphate thymidylyltransferase (RfbA). United States: N. p., 2017. Web. doi:10.1107/S2053230X17015357.
Baumgartner, Jackson, Lee, Jesi, Halavaty, Andrei S., Minasov, George, Anderson, Wayne F., & Kuhn, Misty L. Structure of the Bacillus anthracis dTDP- L -rhamnose-biosynthetic enzyme glucose-1-phosphate thymidylyltransferase (RfbA). United States. doi:10.1107/S2053230X17015357.
Baumgartner, Jackson, Lee, Jesi, Halavaty, Andrei S., Minasov, George, Anderson, Wayne F., and Kuhn, Misty L. Mon . "Structure of the Bacillus anthracis dTDP- L -rhamnose-biosynthetic enzyme glucose-1-phosphate thymidylyltransferase (RfbA)". United States. doi:10.1107/S2053230X17015357.
@article{osti_1408122,
title = {Structure of the Bacillus anthracis dTDP- L -rhamnose-biosynthetic enzyme glucose-1-phosphate thymidylyltransferase (RfbA)},
author = {Baumgartner, Jackson and Lee, Jesi and Halavaty, Andrei S. and Minasov, George and Anderson, Wayne F. and Kuhn, Misty L.},
abstractNote = {L-Rhamnose is a ubiquitous bacterial cell-wall component. The biosynthetic pathway for its precursor dTDP-L-rhamnose is not present in humans, which makes the enzymes of the pathway potential drug targets. In this study, the three-dimensional structure of the first protein of this pathway, glucose-1-phosphate thymidylyltransferase (RfbA), fromBacillus anthraciswas determined. In other organisms this enzyme is referred to as RmlA. RfbA was co-crystallized with the products of the enzymatic reaction, dTDP-α-D-glucose and pyrophosphate, and its structure was determined at 2.3 Å resolution. This is the first reported thymidylyltransferase structure from a Gram-positive bacterium. RfbA shares overall structural characteristics with known RmlA homologs. However, RfbA exhibits a shorter sequence at its C-terminus, which results in the absence of three α-helices involved in allosteric site formation. Consequently, RfbA was observed to exhibit a quaternary structure that is unique among currently reported glucose-1-phosphate thymidylyltransferase bacterial homologs. These structural analyses suggest that RfbA may not be allosterically regulated in some organisms and is structurally distinct from other RmlA homologs.},
doi = {10.1107/S2053230X17015357},
journal = {Acta Crystallographica. Section F, Structural Biology Communications},
number = 11,
volume = 73,
place = {United States},
year = {Mon Oct 30 00:00:00 EDT 2017},
month = {Mon Oct 30 00:00:00 EDT 2017}
}