9HN8

Apo Structure of Truncated 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis

Summary for 9HN8

• Entry DOI: 10.2210/pdb9hn8/pdb
• Descriptor: 1-deoxy-D-xylulose-5-phosphate synthase (2 entities in total)
• Functional Keywords: apo, thiamine-dependent enzyme, synthase, transferase
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 2
• Total formula weight: 127246.16

Authors

Gawriljuk, V.O.,Groves, M.R. (deposition date: 2024-12-10, release date: 2025-01-22)

Primary citation

Gawriljuk, V.O.,Alhayek, A.,Hirsch, A.K.H.,Groves, M.R.
Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design.
Biochem.Biophys.Res.Commun., 747:151246-151246, 2025

PubMed Abstract: The 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.

PubMed: 39793397
DOI: 10.1016/j.bbrc.2024.151246

Experimental method

X-RAY DIFFRACTION (2.65 Å)