2huu
|
Crystal structure of Aedes aegypti alanine glyoxylate aminotransferase in complex with alanine
OverviewOverview
Mosquitoes are unique in having evolved two alanine glyoxylate, aminotransferases (AGTs). One is 3-hydroxykynurenine transaminase (HKT), which is primarily responsible for catalyzing the transamination of, 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). Interestingly, XA is, used by malaria parasites as a chemical trigger for their development, within the mosquito. This 3-HK to XA conversion is considered the major, mechanism mosquitoes use to detoxify the chemically reactive and, potentially toxic 3-HK. The other AGT is a typical dipteran insect AGT and, is specific for converting glyoxylic acid to glycine. Here we report the, 1.75A high-resolution three-dimensional crystal structure of AGT from the, mosquito Aedes aegypti (AeAGT) and structures of its complexes with, reactants glyoxylic acid and alanine at 1.75 and 2.1A resolution, respectively. This is the first time that the three-dimensional crystal, structures of an AGT with its amino acceptor, glyoxylic acid, and amino, donor, alanine, have been determined. The protein is dimeric and adopts, the type I-fold of pyridoxal 5-phosphate (PLP)-dependent, aminotransferases. The PLP co-factor is covalently bound to the active, site in the crystal structure, and its binding site is similar to those of, other AGTs. The comparison of the AeAGT-glyoxylic acid structure with, other AGT structures revealed that these glyoxylic acid binding residues, are conserved in most AGTs. Comparison of the AeAGT-alanine structure with, that of the Anopheles HKT-inhibitor complex suggests that a Ser-Asn-Phe, motif in the latter may be responsible for the substrate specificity of, HKT enzymes for 3-HK.
About this StructureAbout this Structure
2HUU is a Single protein structure of sequence from Aedes aegypti with and as ligands. Active as Alanine--glyoxylate transaminase, with EC number 2.6.1.44 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase., Han Q, Robinson H, Gao YG, Vogelaar N, Wilson SR, Rizzi M, Li J, J Biol Chem. 2006 Dec 1;281(48):37175-82. Epub 2006 Sep 21. PMID:16990263
Page seeded by OCA on Tue Jan 29 20:29:24 2008