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Functional and structural characterization of an ECF-type ABC transporter for vitamin B12

Vitamin B12 (cobalamin) is the most complex B-type vitamin and is synthetized exclusively in a limited number of prokaryotes. Its biologically active variants contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways such as L-methionine synthesis and ri...

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Autores principales: Santos, Joana A, Rempel, Stephan, Mous, Sandra TM, Pereira, Cristiane T, ter Beek, Josy, de Gier, Jan-Willem, Guskov, Albert, Slotboom, Dirk J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997447/
https://www.ncbi.nlm.nih.gov/pubmed/29809140
http://dx.doi.org/10.7554/eLife.35828
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author Santos, Joana A
Rempel, Stephan
Mous, Sandra TM
Pereira, Cristiane T
ter Beek, Josy
de Gier, Jan-Willem
Guskov, Albert
Slotboom, Dirk J
author_facet Santos, Joana A
Rempel, Stephan
Mous, Sandra TM
Pereira, Cristiane T
ter Beek, Josy
de Gier, Jan-Willem
Guskov, Albert
Slotboom, Dirk J
author_sort Santos, Joana A
collection PubMed
description Vitamin B12 (cobalamin) is the most complex B-type vitamin and is synthetized exclusively in a limited number of prokaryotes. Its biologically active variants contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways such as L-methionine synthesis and ribonucleotide reduction. Although its biosynthesis and role as co-factor are well understood, knowledge about uptake of cobalamin by prokaryotic auxotrophs is scarce. Here, we characterize a cobalamin-specific ECF-type ABC transporter from Lactobacillus delbrueckii, ECF-CbrT, and demonstrate that it mediates the specific, ATP-dependent uptake of cobalamin. We solved the crystal structure of ECF-CbrT in an apo conformation to 3.4 Å resolution. Comparison with the ECF transporter for folate (ECF-FolT2) from the same organism, reveals how the identical ECF module adjusts to interact with the different substrate binding proteins FolT2 and CbrT. ECF-CbrT is unrelated to the well-characterized B12 transporter BtuCDF, but their biochemical features indicate functional convergence.
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spelling pubmed-59974472018-06-13 Functional and structural characterization of an ECF-type ABC transporter for vitamin B12 Santos, Joana A Rempel, Stephan Mous, Sandra TM Pereira, Cristiane T ter Beek, Josy de Gier, Jan-Willem Guskov, Albert Slotboom, Dirk J eLife Biochemistry and Chemical Biology Vitamin B12 (cobalamin) is the most complex B-type vitamin and is synthetized exclusively in a limited number of prokaryotes. Its biologically active variants contain rare organometallic bonds, which are used by enzymes in a variety of central metabolic pathways such as L-methionine synthesis and ribonucleotide reduction. Although its biosynthesis and role as co-factor are well understood, knowledge about uptake of cobalamin by prokaryotic auxotrophs is scarce. Here, we characterize a cobalamin-specific ECF-type ABC transporter from Lactobacillus delbrueckii, ECF-CbrT, and demonstrate that it mediates the specific, ATP-dependent uptake of cobalamin. We solved the crystal structure of ECF-CbrT in an apo conformation to 3.4 Å resolution. Comparison with the ECF transporter for folate (ECF-FolT2) from the same organism, reveals how the identical ECF module adjusts to interact with the different substrate binding proteins FolT2 and CbrT. ECF-CbrT is unrelated to the well-characterized B12 transporter BtuCDF, but their biochemical features indicate functional convergence. eLife Sciences Publications, Ltd 2018-05-29 /pmc/articles/PMC5997447/ /pubmed/29809140 http://dx.doi.org/10.7554/eLife.35828 Text en © 2018, Santos et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Santos, Joana A
Rempel, Stephan
Mous, Sandra TM
Pereira, Cristiane T
ter Beek, Josy
de Gier, Jan-Willem
Guskov, Albert
Slotboom, Dirk J
Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title_full Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title_fullStr Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title_full_unstemmed Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title_short Functional and structural characterization of an ECF-type ABC transporter for vitamin B12
title_sort functional and structural characterization of an ecf-type abc transporter for vitamin b12
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997447/
https://www.ncbi.nlm.nih.gov/pubmed/29809140
http://dx.doi.org/10.7554/eLife.35828
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