Structural highlights
FunctionDXS_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 PubMedThe enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme. Comparisons with other homologous DXPS structures highlight a similar dynamic response to cofactor absence. Despite the increased flexibility, key residues for the activity and ThDP binding retain their positions, preserving the structural integrity of the catalytic core. These findings demonstrate the critical role of ThDP in maintaining DXPS stability and suggest that dynamic structural changes in the apo state may influence inhibitor binding targeting the cofactor site. Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.,Gawriljuk VO, Alhayek A, Hirsch AKH, Groves MR Biochem Biophys Res Commun. 2025 Feb 2;747:151246. doi: , 10.1016/j.bbrc.2024.151246. Epub 2025 Jan 4. PMID:39793397[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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This page was last modified 10:24, 22 January 2025.