%0 Journal Article
%@ 1879-0003
%A Karan, Sumita
%A Pratap, Bhanu
%A Ashish, .
%A Saxena, Ajay K
%D 2019
%F open:2344
%I Elsevier Science
%J International journal of biological macromolecules
%K 7-Bisphosphate phosphatase; CD; GDP-heptose biosynthetic pathway; M. tuberculosisd-glycero-d-manno-heptose-1; Molecular modeling and dynamics simulation; SAXS
%P 676-685
%T Low-resolution SAXS and structural dynamics analysis on M. tuberculosis GmhB enzyme involved in GDP-heptose biosynthetic pathway.
%U http://crdd.osdd.net/open/2344/
%V 136
%X The M. tuberculosis GmhB protein converts the d-glycero-α-d-manno-heptose 1,7-bisphosphate (GMB) intermediate into d-glycero-α-d-manno-heptose 1-phosphate by removing the phosphate group at the C-7 position. To understand the structure and substrate binding mechanism, the MtbGmhB was purified which elutes as monomer on gel filtration column. The small angle x-ray scattering analysis shows that MtbGmhB forms fully folded monomer with shape profile similar to its modeled structure. The circular dichroism analysis shows 38% α-helix, 15% β-sheets and 47% random coil structures in MtbGmhB, similar to haloalkanoic acid dehalogenase (HAD) phosphohydrolase enzymes. The modeled MtbGmhB structure shows the catalytic site, which forms a concave, semicircular surface using the three loops around GMB substrate binding site. Dynamic simulation analysis on (i) Apo (ii) GMB bound (iii) GMB + Mg bound (iv) Zn +GMB + Mg bound MtbGmhB structures show that Zn as well as Mg ions stabilize the loop conformation and trigger the changes in GMB substrate binding to active site of MtbGmhB. Upon demetallization, the large conformational changes occurred in ions binding loops, and leads to difference in GMB substrate binding to MtbGmhB. Our study provides information about structure and substrate binding of MtbGmhB, which may contribute in therapeutic development against M. tuberculosis.
%Z Copyright of this article belongs to Elsevier Science.