2HUU

Crystal structure of Aedes aegypti alanine glyoxylate aminotransferase in complex with alanine

Summary for 2HUU

• Entry DOI: 10.2210/pdb2huu/pdb
• Related: 2HUF 2HUI
• Descriptor: Alanine glyoxylate aminotransferase, ALANINE, 1-BUTANOL, ... (4 entities in total)
• Functional Keywords: alpha and beta protein, plp-dependent transferase, transferase
• Biological source: Aedes aegypti (yellow fever mosquito)
• Total number of polymer chains: 2
• Total formula weight: 86944.89

Authors

Han, Q.,Robinson, H.,Gao, Y.G.,Vogelaar, N.,Wilson, S.R.,Rizzi, M.,Li, J. (deposition date: 2006-07-27, release date: 2006-09-26, Last modification date: 2023-11-15)

Primary citation

Han, Q.,Robinson, H.,Gao, Y.G.,Vogelaar, N.,Wilson, S.R.,Rizzi, M.,Li, J.
Crystal Structures of Aedes aegypti Alanine Glyoxylate Aminotransferase.
J.Biol.Chem., 281:37175-37182, 2006

PubMed 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 1.75A 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.

PubMed: 16990263
DOI: 10.1074/jbc.M607032200

Experimental method

X-RAY DIFFRACTION (2.1 Å)