Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase

Qian Han, Howard Robinson, Gui Gao Yi, Nancy Vogelaar, Scott R. Wilson, Menico Rizzi, Jianyong Li

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

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 1.75 Å high-resolution three-dimensional crystal structure ofAGTfrom the mosquito Aedes aegypti (AeAGT) and structures of its complexes with reactants glyoxylic acid and alanine at 1.75 and 2.1 Å 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.

Lingua originaleInglese
pagine (da-a)37175-37182
Numero di pagine8
RivistaJournal of Biological Chemistry
Volume281
Numero di pubblicazione48
DOI
Stato di pubblicazionePubblicato - 1 dic 2006

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