3ntj

Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase

spinqualitylabelsall models 3ntj, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ntj is a 4 chain structure with sequence from Plasmodium falciparum 3D7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function OAT_PLAF7 The enzyme has a very narrow substrate specificity and can only catalyze the transamination of alpha-ketoglutarate with ornithine or N-acetylornithine and of glutamate-5-semialdehyde with glutamate and alanine. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Ornithine delta-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 A 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. Redox regulation of Plasmodium falciparum ornithine delta-aminotransferase.,Jortzik E, Fritz-Wolf K, Sturm N, Hipp M, Rahlfs S, Becker K J Mol Biol. 2010 Sep 17;402(2):445-59. Epub 2010 Jul 29. PMID:20673832 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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