TY - JOUR
T1 - Crystal structure of D-glycero-α-D-manno-heptose-1-phosphate guanylyltransferase from Yersinia pseudotuberculosis
AU - Kim, Hyojin
AU - Park, Jimin
AU - Kim, Suwon
AU - Shin, Dong Hae
N1 - Funding Information:
We are grateful to the staffs at both Pohang Light Source and Advanced Light Source. This work was supported by the Basic Science Research Program ( 2015R1D1A1A01058942 ) funded by the National Research Foundation of Korea grant granted by the Ministry of Education, Science and Technology , Republic of Korea (MEST). J. Park was supported by Brain Korea 21 (BK21) Project.
Publisher Copyright:
© 2017
PY - 2018/3
Y1 - 2018/3
N2 - The Gram-negative bacterium Yersinia pseudotuberculosis is the causative agent of yersiniosis. D-glycero-α-D-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme of the GDP-D-glycero-α-D-manno-heptose biosynthesis pathway which is important for the virulence of the microorganism. Therefore, HddC is a potential target of antibiotics against yersiniosis. In this study, HddC from the synthesized HddC gene of Y. pseudotuberculosis has been expressed, purified, crystallized. Synchrotron X-ray data from a selenomethionine-substituted HddC crystal were also collected and its structure was determined at 2.0 Å resolution. Structure analyses revealed that it belongs to the glycosyltransferase A type superfamily members with the signature motif GXGXR for nucleotide binding. Despite of remarkable structural similarity, HddC uses GTP for catalysis instead of CTP and UTP which are used for other major family members, cytidylyltransferase and uridylyltransferase, respectively. We suggest that EXXPLGTGGA and L(S/A/G)X(S/G) motifs are probably essential to bind with GTP and a FSFE motif with substrate.
AB - The Gram-negative bacterium Yersinia pseudotuberculosis is the causative agent of yersiniosis. D-glycero-α-D-manno-heptose-1-phosphate guanylyltransferase (HddC) is the fourth enzyme of the GDP-D-glycero-α-D-manno-heptose biosynthesis pathway which is important for the virulence of the microorganism. Therefore, HddC is a potential target of antibiotics against yersiniosis. In this study, HddC from the synthesized HddC gene of Y. pseudotuberculosis has been expressed, purified, crystallized. Synchrotron X-ray data from a selenomethionine-substituted HddC crystal were also collected and its structure was determined at 2.0 Å resolution. Structure analyses revealed that it belongs to the glycosyltransferase A type superfamily members with the signature motif GXGXR for nucleotide binding. Despite of remarkable structural similarity, HddC uses GTP for catalysis instead of CTP and UTP which are used for other major family members, cytidylyltransferase and uridylyltransferase, respectively. We suggest that EXXPLGTGGA and L(S/A/G)X(S/G) motifs are probably essential to bind with GTP and a FSFE motif with substrate.
KW - D-glycero-α-D-manno-heptose-1-phosphate guanylyltransferase (HddC)
KW - GDP-D-glycero-α-D-manno-heptose biosynthesis pathway
KW - Glycosyltransferase a type superfamilyl
KW - X-ray crystal structure
KW - Yersiniosis
UR - http://www.scopus.com/inward/record.url?scp=85039932977&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2017.12.005
DO - 10.1016/j.bbapap.2017.12.005
M3 - Article
C2 - 29277661
AN - SCOPUS:85039932977
SN - 1570-9639
VL - 1866
SP - 482
EP - 487
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 3
ER -