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Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS
 
Creator Shinde, R N
Karthikeyan, Subramanian
Singh, Balvinder
 
Subject QR Microbiology
 
Description 3,4-dihydroxy-2-butanone-4-phosphate synthase (DHBPS) catalyzes the conversion of D-ribulose 5-phosphate (Ru5P) to L-3,4-dihydroxy-2-butanone-4-phosphate in the presence of Mg2+. Although crystal structures of DHBPS in complex with Ru5P and non-catalytic metal ions have been reported, structure with Ru5P along with Mg2+ is still elusive. Therefore, mechanistic role played by Mg2+ in the structure of DHBPS is poorly understood. In this study, molecular dynamics simulations of DHBPS-Ru5P complex along with Mg2+ have shown entry of Mg2+ from bulk solvent into active site. Presence of Mg2+ in active site has constrained conformations of Ru5P and has reduced flexibility of loop-2. Formation of hydrogen bonds among Thr-108 and residues - Gly-109, Val-110, Ser-111, and Asp-114 are found to be critical for entry of Mg2+ into active site. Subsequent in silico mutations of residues, Thr-108 and Asp-114 have substantiated the importance of these interactions. Loop-4 of one monomer is being proposed to act as a “lid” covering the active site of other monomer. Further, the conserved nature of residues taking part in the transfer of Mg2+ suggests the same mechanism being present in DHBPS of other microorganisms. Thus, this study provides insights into the functioning of DHBPS that can be used for the designing of inhibitors.
 
Date 2017
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1992/1/subra.pdf
Shinde, R N and Karthikeyan, Subramanian and Singh, Balvinder (2017) Molecular dynamics studies unravel role of conserved residues responsible for movement of ions into active site of DHBPS. Scientific Reports, 7. p. 40452. ISSN 2045-2322
 
Relation http://dx.doi.org/10.1038/srep40452
http://crdd.osdd.net/open/1992/