7a9h | pdb_00007a9h

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

spinqualitylabelsall models 7a9h, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7a9h is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.849Å Ligands: MG, TPP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DXS_MYCTU Catalyzes the acyloin condensation reaction between C atoms 2 and 3 of pyruvate and glyceraldehyde 3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate (DXP). Publication Abstract from PubMed 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. First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.,Gierse RM, Oerlemans R, Reddem ER, Gawriljuk VO, Alhayek A, Baitinger D, Jakobi H, Laber B, Lange G, Hirsch AKH, Groves MR Sci Rep. 2022 May 4;12(1):7221. doi: 10.1038/s41598-022-11205-9. PMID:35508530 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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