9IJB

Crystal structure and function analysis of a highly potential drug target 6-phosphogluconate dehydrogenase in Mycobacterium tuberculosis

Summary for 9IJB

• Entry DOI: 10.2210/pdb9ijb/pdb
• Descriptor: 6-phosphogluconate dehydrogenase, NAD(+)-dependent, decarboxylating (2 entities in total)
• Functional Keywords: tecramer, dehydrogenase enzyme, nad binding, pentose phosphate pathway, hydrolase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 4
• Total formula weight: 145600.30

Authors

Wang, Y.Z.,Ren, X.Q.,Li, T.,Zhang, R.D. (deposition date: 2024-06-22, release date: 2024-07-03, Last modification date: 2024-08-07)

Primary citation

Wang, Y.,Ren, X.,Li, T.,Su, D.,Zhang, R.
Crystal structure and function analysis of 6-phosphogluconate dehydrogenase in Mycobacterium tuberculosis.
Biochem.Biophys.Res.Commun., 731:150390-150390, 2024

PubMed Abstract: 6-phosphogluconate dehydrogenase (6PGDH) is an essential enzyme in energy metabolism and redox reactions, and represents a potential drug target for the development of therapies targeting trypanosomes, plasmodium, or other pathogens. Tuberculosis, caused by Mycobacterium tuberculosis, is a contagious disease that severely affects human health, with approximately one-third of the world's population infected. However, the protein structure, exact oligomeric state, and catalytic mechanism of 6PGDH in Mycobacterium tuberculosis (Mt6PGDH) have remained largely unknown. In this study, we successfully purified and determined the structure of Mt6PGDH, revealing its function as a tetramer in both solution and crystal states. Through structural comparisons, we clarified the tetramer formation mechanism and the oligomeric organization of short-chain 6PGDHs. Additionally, we identified key residues for coenzyme recognition and catalytic activity. This work not only deepens our understanding of the enzymatic function of Mt6PGDH but also lays a foundation for the development of drugs targeting this enzyme.

PubMed: 39024980
DOI: 10.1016/j.bbrc.2024.150390

Experimental method

X-RAY DIFFRACTION (2.7404051296 Å)