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GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis
d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme synthesizing a building component of lipopolysaccharide (LPS) of Gram-negative bacteria. Since HddC is a potential new target to develop antibiotics, the analysis of the structural and functional relationship of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981941/ https://www.ncbi.nlm.nih.gov/pubmed/31906195 http://dx.doi.org/10.3390/ijms21010280 |
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author | Kim, Suwon Kim, Mi-Sun Jo, Seri Shin, Dong Hae |
author_facet | Kim, Suwon Kim, Mi-Sun Jo, Seri Shin, Dong Hae |
author_sort | Kim, Suwon |
collection | PubMed |
description | d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme synthesizing a building component of lipopolysaccharide (LPS) of Gram-negative bacteria. Since HddC is a potential new target to develop antibiotics, the analysis of the structural and functional relationship of the complex structure will lead to a better idea to design inhibitory compounds. X-ray crystallography and biochemical experiments to elucidate the guanine preference were performed based on the multiple sequence alignment. The crystal structure of HddC from Yersinia pseudotuberculosis (YPT) complexed with guanosine 5′-(β-amino)-diphosphate (GMPPN) has been determined at 1.55 Å resolution. Meanwhile, the mutants revealed their reduced guanine affinity, instead of acquiring noticeable pyrimidine affinity. The complex crystal structure revealed that GMPPN is docked in the catalytic site with the aid of Glu80 positioning on the conserved motif EXXPLGTGGA. In the HddC family, this motif is expected to recruit nucleotides through interacting with bases. The crystal structure shows that oxygen atoms of Glu80 forming two hydrogen bonds play a critical role in interaction with two nitrogen atoms of the guanine base of GMPPN. Interestingly, the binding of GMPPN induced the formation of an oxyanion hole-like conformation on the L(S/A/G)X(S/G) motif and consequently influenced on inducing a conformational shift of the region around Ser55. |
format | Online Article Text |
id | pubmed-6981941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69819412020-02-07 GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis Kim, Suwon Kim, Mi-Sun Jo, Seri Shin, Dong Hae Int J Mol Sci Article d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme synthesizing a building component of lipopolysaccharide (LPS) of Gram-negative bacteria. Since HddC is a potential new target to develop antibiotics, the analysis of the structural and functional relationship of the complex structure will lead to a better idea to design inhibitory compounds. X-ray crystallography and biochemical experiments to elucidate the guanine preference were performed based on the multiple sequence alignment. The crystal structure of HddC from Yersinia pseudotuberculosis (YPT) complexed with guanosine 5′-(β-amino)-diphosphate (GMPPN) has been determined at 1.55 Å resolution. Meanwhile, the mutants revealed their reduced guanine affinity, instead of acquiring noticeable pyrimidine affinity. The complex crystal structure revealed that GMPPN is docked in the catalytic site with the aid of Glu80 positioning on the conserved motif EXXPLGTGGA. In the HddC family, this motif is expected to recruit nucleotides through interacting with bases. The crystal structure shows that oxygen atoms of Glu80 forming two hydrogen bonds play a critical role in interaction with two nitrogen atoms of the guanine base of GMPPN. Interestingly, the binding of GMPPN induced the formation of an oxyanion hole-like conformation on the L(S/A/G)X(S/G) motif and consequently influenced on inducing a conformational shift of the region around Ser55. MDPI 2019-12-31 /pmc/articles/PMC6981941/ /pubmed/31906195 http://dx.doi.org/10.3390/ijms21010280 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Suwon Kim, Mi-Sun Jo, Seri Shin, Dong Hae GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title | GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title_full | GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title_fullStr | GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title_full_unstemmed | GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title_short | GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis |
title_sort | gtp preference of d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase from yersinia pseudotuberculosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981941/ https://www.ncbi.nlm.nih.gov/pubmed/31906195 http://dx.doi.org/10.3390/ijms21010280 |
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