7A9H

Truncated 1-deoxy-D-xylulose 5-phosphate synthase (DXS) from Mycobacterium tuberculosis

This is a non-PDB format compatible entry.

Summary for 7A9H

• Entry DOI: 10.2210/pdb7a9h/pdb
• Related: 7A9G
• Descriptor: 1-deoxy-D-xylulose-5-phosphate synthase,1-deoxy-D-xylulose-5-phosphate synthase, MAGNESIUM ION, THIAMINE DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: transferase
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 2
• Total formula weight: 134280.16

Authors

Gierse, R.M.,Reddem, E.,Grooves, M.R. (deposition date: 2020-09-02, release date: 2022-03-23, Last modification date: 2024-01-31)

Primary citation

Gierse, R.M.,Oerlemans, R.,Reddem, E.R.,Gawriljuk, V.O.,Alhayek, A.,Baitinger, D.,Jakobi, H.,Laber, B.,Lange, G.,Hirsch, A.K.H.,Groves, M.R.
First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.
Sci Rep, 12:7221-7221, 2022

PubMed Abstract: The development of drug resistance by Mycobacterium tuberculosis and other pathogenic bacteria emphasizes the need for new antibiotics. Unlike animals, most bacteria synthesize isoprenoid precursors through the MEP pathway. 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS) catalyzes the first reaction of the MEP pathway and is an attractive target for the development of new antibiotics. We report here the successful use of a loop truncation to crystallize and solve the first DXPS structures of a pathogen, namely M. tuberculosis (MtDXPS). The main difference found to other DXPS structures is in the active site where a highly coordinated water was found, showing a new mechanism for the enamine-intermediate stabilization. Unlike other DXPS structures, a "fork-like" motif could be identified in the enamine structure, using a different residue for the interaction with the cofactor, potentially leading to a decrease in the stability of the intermediate. In addition, electron density suggesting a phosphate group could be found close to the active site, provides new evidence for the D-GAP binding site. These results provide the opportunity to improve or develop new inhibitors specific for MtDXPS through structure-based drug design.

PubMed: 35508530
DOI: 10.1038/s41598-022-11205-9

Experimental method

X-RAY DIFFRACTION (1.849 Å)