Crystal Structures of Aedes Aegypt Alanine Glyoxylate Aminotransferase

Journal Article · Sun Jan 01 04:00:00 EST 2006 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M607032200· OSTI ID:930205

Han, Q; Robinson, H; Gao, Y; Vogelaar, N; Wilson, S; Rizzi, M; Li, J

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{angstrom} 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 2.1{angstrom} 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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 930205
• Report Number(s): BNL--80868-2008-JA
• Journal Information: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Vol. 281; ISSN 0021-9258; ISSN JBCHA3
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ALANINES
AMINOTRANSFERASES
COMPLEXES
CONVERSION
CRYSTAL STRUCTURE
ENZYMES
GLYCINE
GLYOXYLIC ACID
INSECTS
MALARIA
MOSQUITOES
PARASITES
PROTEINS
PYRIDOXAL
RESIDUES
RESOLUTION
SPECIFICITY
SUBSTRATES
USES
national synchrotron light source