Structural Basis of Glycerophosphodiester Recognition
by the Mycobacterium tuberculosis Substrate-Binding
Protein UgpB
Version 2 2019-08-29, 14:33
Version 1 2019-08-21, 14:40
Posted on 2019-08-29 - 14:33
Mycobacterium tuberculosis (Mtb) is the
causative agent of tuberculosis (TB) and has evolved an
incredible ability to survive latently within the human host for decades.
The Mtb pathogen encodes for a low number of ATP-binding
cassette (ABC) importers for the acquisition of carbohydrates that
may reflect the nutrient poor environment within the host macrophages. Mtb UgpB (Rv2833c) is the substrate binding domain of the
UgpABCE transporter that recognizes glycerophosphocholine (GPC), indicating
that this transporter has a role in recycling glycerophospholipid
metabolites. By using a combination of saturation transfer difference
(STD) NMR and X-ray crystallography, we report the structural analysis
of Mtb UgpB complexed with GPC and have identified
that Mtb UgpB not only recognizes GPC but is also
promiscuous for a broad range of glycerophosphodiesters. Complementary
biochemical analyses and site-directed mutagenesis precisely define
the molecular basis and specificity of glycerophosphodiester recognition.
Our results provide critical insights into the structural and functional
role of the Mtb UgpB transporter and reveal that
the specificity of this ABC-transporter is not limited to GPC, therefore
optimizing the ability of Mtb to scavenge scarce
nutrients and essential glycerophospholipid metabolites via a single
transporter during intracellular infection.
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Fenn, Jonathan
S.; Nepravishta, Ridvan; Guy, Collette S.; Harrison, James; Angulo, Jesus; Cameron, Alexander D.; et al. (2019). Structural Basis of Glycerophosphodiester Recognition
by the Mycobacterium tuberculosis Substrate-Binding
Protein UgpB. ACS Publications. Collection. https://doi.org/10.1021/acschembio.9b00204
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AUTHORS (7)
JF
Jonathan
S. Fenn
RN
Ridvan Nepravishta
CG
Collette S. Guy
JH
James Harrison
JA
Jesus Angulo
AC
Alexander D. Cameron
EF
Elizabeth Fullam