3LG0

Structure of Plasmodium falciparum ornithine delta-aminotransferase

Summary for 3LG0

• Entry DOI: 10.2210/pdb3lg0/pdb
• Descriptor: Ornithine aminotransferase (2 entities in total)
• Functional Keywords: activation of plasmodium falciparum ornithine delta-aminotransferase, delta-aminotransferase, pyridoxal-5-phosphate-dependent enzyme, ornithine, alpha-ketoglutarate, plasmodium falciparum, aminotransferase, pyridoxal phosphate, transferase
• Biological source: Plasmodium falciparum
• Cellular location: Cytoplasm (Probable): Q07805
• Total number of polymer chains: 4
• Total formula weight: 188728.74

Authors

Fritz-Wolf, K.,Jortzik, E.,Stumpf, M.,Becker, K. (deposition date: 2010-01-19, release date: 2010-08-04, Last modification date: 2023-09-06)

Primary citation

Jortzik, E.,Fritz-Wolf, K.,Sturm, N.,Hipp, M.,Rahlfs, S.,Becker, K.
Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase.
J.Mol.Biol., 402:445-459, 2010

PubMed Abstract: Ornithine δ-aminotransferase (OAT) of the malaria parasite Plasmodium falciparum catalyzes the reversible conversion of ornithine into glutamate-5-semialdehyde and glutamate and is-in contrast to its human counterpart-activated by thioredoxin (Trx) by a factor of 10. Trx, glutaredoxin, and plasmoredoxin are redox-active proteins that play a crucial role in the maintenance and control of redox reactions, and were shown to interact with P. falciparum OAT. OAT, which is involved in ornithine homeostasis and proline biosynthesis, is essential for mitotic cell division in rapidly growing cells, thus representing a potential target for chemotherapeutic intervention. Here we report the three-dimensional crystal structure of P. falciparum OAT at 2.3 Å resolution. The overall structure is very similar to that of the human OAT. However, in plasmodial OAT, the loop involved in substrate binding contains two cysteine residues, which are lacking in human OAT. Site-directed mutagenesis of these cysteines and functional analysis demonstrated that Cys154 and Cys163 mediate the interaction with Trx. Interestingly, the Cys154→Ser mutant has a strongly reduced specific activity, most likely due to impaired binding of ornithine. Cys154 and Cys163 are highly conserved in Plasmodium but do not exist in other organisms, suggesting that redox regulation of OAT by Trx is specific for malaria parasites. Plasmodium might require a tight Trx-mediated control of OAT activity for coordinating ornithine homeostasis, polyamine synthesis, proline synthesis, and mitotic cell division.

PubMed: 20673832
DOI: 10.1016/j.jmb.2010.07.039

Experimental method

X-RAY DIFFRACTION (2.3 Å)