4QFH

Structure of a glucose-6-phosphate isomerase from Trypanosoma cruzi

Summary for 4QFH

• Entry DOI: 10.2210/pdb4qfh/pdb
• Descriptor: Glucose-6-phosphate isomerase, 6-O-phosphono-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: ssgcid, glucose-6-phosphate isomerase, trypanosoma cruzi, human american trypanosomiasis, chagas disease, structural genomics, seattle structural genomics center for infectious disease, isomerase
• Biological source: Trypanosoma cruzi
• Total number of polymer chains: 2
• Total formula weight: 139480.40

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2014-05-21, release date: 2014-06-18, Last modification date: 2026-03-04)

Primary citation

Austin, K.,Obachi, V.A.,Muzenda, F.L.,Moetlediwa, M.T.,Agyei, C.,Craig, T.,Abendroth, J.,Edwards, T.,Nguyen, M.,Tran, N.,Staker, B.,Subramanian, S.,Myler, P.,Zininga, T.,Govender, K.K.,Chakafana, G.
Structural Characterization of Glycolytic Enzymes from Trypanosoma cruzi.
Mol.Biochem.Parasitol., :111736-111736, 2026

PubMed Abstract: Trypanosoma cruzi, the etiological agent of Chagas disease, depends on glycolysis for ATP production, rendering its glycolytic enzymes attractive targets for therapeutic development. Here, we report the high-resolution crystal structures of two essential glycolytic enzymes, glucose-6-phosphate isomerase (Tc PGI, 1.8 Å) and enolase (Tc enolase, 2.4 Å) and provide structural and computational analyses to support structure-based drug design. Tc PGI adopts a dimeric αβα sandwich fold and features a parasite-specific 53-residue N-terminal extension and a unique C-terminal hook region which both distinguish it from its human ortholog. Tc enolase exhibits the conserved (α/β) 8 TIM barrel fold but harbors minor distinct structural deviations, including an extended α17 helix and a structured α1 region, which differentiate it from human isoforms. Both enzymes exhibited high thermal stability, consistent with adaptation to the parasite's complex life cycle. Structure-based virtual screening using a scaffold with known multi-target potential identified distinct high-affinity inhibitors for each enzyme. Molecular dynamics simulations further confirmed stable enzyme-inhibitor interactions and favorable binding energetics. Collectively, these findings reveal structural signatures unique to T. cruzi glycolytic enzymes and lay the groundwork for the development of antiparasitic therapeutics.

PubMed: 41713750
DOI: 10.1016/j.molbiopara.2026.111736

Experimental method

X-RAY DIFFRACTION (1.8 Å)