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Article

GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis

Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52, Ewhayeodae-gil, Seoul 03760, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(1), 280; https://doi.org/10.3390/ijms21010280
Submission received: 25 November 2019 / Revised: 23 December 2019 / Accepted: 24 December 2019 / Published: 31 December 2019
(This article belongs to the Section Molecular Microbiology)

Abstract

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.
Keywords: d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC); Yersinia pseudotuberculosis (YPT); guanosine-5′-(β-amino)-diphosphate (GMPPN); guanine specificity; antibiotics d-glycero-α-d-manno-heptose-1-phosphate guanylyltransferase (HddC); Yersinia pseudotuberculosis (YPT); guanosine-5′-(β-amino)-diphosphate (GMPPN); guanine specificity; antibiotics

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MDPI and ACS Style

Kim, S.; Kim, M.-S.; Jo, S.; Shin, D.H. GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis. Int. J. Mol. Sci. 2020, 21, 280. https://doi.org/10.3390/ijms21010280

AMA Style

Kim S, Kim M-S, Jo S, Shin DH. GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis. International Journal of Molecular Sciences. 2020; 21(1):280. https://doi.org/10.3390/ijms21010280

Chicago/Turabian Style

Kim, Suwon, Mi-Sun Kim, Seri Jo, and Dong Hae Shin. 2020. "GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis" International Journal of Molecular Sciences 21, no. 1: 280. https://doi.org/10.3390/ijms21010280

APA Style

Kim, S., Kim, M.-S., Jo, S., & Shin, D. H. (2020). GTP Preference of d-Glycero-α-d-manno-Heptose-1-Phosphate Guanylyltransferase from Yersinia pseudotuberculosis. International Journal of Molecular Sciences, 21(1), 280. https://doi.org/10.3390/ijms21010280

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